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Yang Z, Li N, Cui H, Liu B, Wang X, Zhang L, Wang X, Zheng L, Yang X, Wu S, Hu J, Wen D. Influence of the Interaction between Genetic Factors and Breastfeeding on Children's Weight Status: A Systematic Review. Adv Nutr 2024; 15:100312. [PMID: 39389470 PMCID: PMC11566687 DOI: 10.1016/j.advnut.2024.100312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Revised: 10/04/2024] [Accepted: 10/07/2024] [Indexed: 10/12/2024] Open
Abstract
Breastfeeding may interact with other risk factors and have a combined influence on child growth. This systematic review aimed to examine the interaction between genetic factors and breastfeeding and how their combination is associated with children weight status. Four databases were searched until August 2024, and 8 eligible studies were identified. The fat mass and obesity associated (FTO) and peroxisome proliferator-activated receptor γ2 (PPARG2) genes were the most examined genes. Although the results of interactions between breastfeeding and genetics factors on children's weight status were inconsistent, some of studies reported that breastfeeding or exclusive breastfeeding attenuated the disadvantageous association between the risk alleles of the genes (higher obesity-specific genetic risk score for a multiple-gene study) and overdevelopment of children's body weight. These findings support the WHO recommendations for prolonged breastfeeding and further suggest breastfeeding interventions to prevent childhood obesity may be more effective in populations with a disadvantageous genetic predisposition. This review was registered in PROSPERO as CRD42023448365.
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Affiliation(s)
- Zhe Yang
- Health Sciences Institute, China Medical University, Shenyang, China; Research Center of China Medical University Birth Cohort, China Medical University, Shenyang, China; Liaoning Key Laboratory of Obesity and Glucose/Lipid Associated Metabolic Diseases, China Medical University, Shenyang, China
| | - Na Li
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, China Medical University, Shenyang, China
| | - Hong Cui
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, China Medical University, Shenyang, China
| | - Borui Liu
- Health Sciences Institute, China Medical University, Shenyang, China; Research Center of China Medical University Birth Cohort, China Medical University, Shenyang, China; Liaoning Key Laboratory of Obesity and Glucose/Lipid Associated Metabolic Diseases, China Medical University, Shenyang, China
| | - Xue Wang
- Medical Information Research Department/Library, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Ling Zhang
- Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China
| | - Xiaochuan Wang
- Health Sciences Institute, China Medical University, Shenyang, China; Research Center of China Medical University Birth Cohort, China Medical University, Shenyang, China; Liaoning Key Laboratory of Obesity and Glucose/Lipid Associated Metabolic Diseases, China Medical University, Shenyang, China
| | - Lu Zheng
- Health Sciences Institute, China Medical University, Shenyang, China; Research Center of China Medical University Birth Cohort, China Medical University, Shenyang, China; Liaoning Key Laboratory of Obesity and Glucose/Lipid Associated Metabolic Diseases, China Medical University, Shenyang, China
| | - Xinyue Yang
- Health Sciences Institute, China Medical University, Shenyang, China; Research Center of China Medical University Birth Cohort, China Medical University, Shenyang, China; Liaoning Key Laboratory of Obesity and Glucose/Lipid Associated Metabolic Diseases, China Medical University, Shenyang, China
| | - Shuqi Wu
- Health Sciences Institute, China Medical University, Shenyang, China; Research Center of China Medical University Birth Cohort, China Medical University, Shenyang, China; Liaoning Key Laboratory of Obesity and Glucose/Lipid Associated Metabolic Diseases, China Medical University, Shenyang, China
| | - Jiajin Hu
- Health Sciences Institute, China Medical University, Shenyang, China; Research Center of China Medical University Birth Cohort, China Medical University, Shenyang, China; Liaoning Key Laboratory of Obesity and Glucose/Lipid Associated Metabolic Diseases, China Medical University, Shenyang, China.
| | - Deliang Wen
- Health Sciences Institute, China Medical University, Shenyang, China; Research Center of China Medical University Birth Cohort, China Medical University, Shenyang, China; Liaoning Key Laboratory of Obesity and Glucose/Lipid Associated Metabolic Diseases, China Medical University, Shenyang, China.
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Bowman WS, Schmidt RJ, Sanghar GK, Thompson GR, Ji H, Zeki AA, Haczku A. "Air That Once Was Breath" Part 1: Wildfire-Smoke-Induced Mechanisms of Airway Inflammation - "Climate Change, Allergy and Immunology" Special IAAI Article Collection: Collegium Internationale Allergologicum Update 2023. Int Arch Allergy Immunol 2024; 185:600-616. [PMID: 38452750 PMCID: PMC11487202 DOI: 10.1159/000536578] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Accepted: 01/23/2024] [Indexed: 03/09/2024] Open
Abstract
BACKGROUND Wildfires are a global concern due to their wide-ranging environmental, economic, and public health impacts. Climate change contributes to an increase in the frequency and intensity of wildfires making smoke exposure a more significant and recurring health concern for individuals with airway diseases. Some of the most prominent effects of wildfire smoke exposure are asthma exacerbations and allergic airway sensitization. Likely due to the delayed recognition of its health impacts in comparison with cigarette smoke and industrial or traffic-related air pollution, research on the composition, the mechanisms of toxicity, and the cellular/molecular pathways involved is poor or non-existent. SUMMARY This review discusses potential underlying pathological mechanisms of wildfire-smoke-related allergic airway disease and asthma. We focused on major gaps in understanding the role of wildfire smoke composition in the development of airway disease and the known and potential mechanisms involving cellular and molecular players of oxidative injury at the epithelial barrier in airway inflammation. We examine how PM2.5, VOCs, O3, endotoxin, microbes, and toxic gases may affect oxidative stress and inflammation in the respiratory mucosal barrier. We discuss the role of AhR in mediating smoke's effects in alarmin release and IL-17A production and how glucocorticoid responsiveness may be impaired by IL-17A-induced signaling and epigenetic changes leading to steroid-resistant severe airway inflammation. KEY MESSAGE Effective mitigation of wildfire-smoke-related respiratory health effects would require comprehensive research efforts aimed at a better understanding of the immune regulatory effects of wildfire smoke in respiratory health and disease.
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Affiliation(s)
- Willis S. Bowman
- UC Davis Lung Center, University of California, Davis, CA, USA
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, School of Medicine, Sacramento, CA, USA
| | - Rebecca J. Schmidt
- Department of Public Health Sciences, School of Medicine, Sacramento, CA, USA
| | - Gursharan K. Sanghar
- UC Davis Lung Center, University of California, Davis, CA, USA
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, School of Medicine, Sacramento, CA, USA
| | - George R. Thompson
- UC Davis Lung Center, University of California, Davis, CA, USA
- Division of Infectious Diseases, Department of Medicine, School of Medicine, Sacramento, CA, USA
| | - Hong Ji
- UC Davis Lung Center, University of California, Davis, CA, USA
- Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, Davis, CA, USA
| | - Amir A. Zeki
- UC Davis Lung Center, University of California, Davis, CA, USA
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, School of Medicine, Sacramento, CA, USA
| | - Angela Haczku
- UC Davis Lung Center, University of California, Davis, CA, USA
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, School of Medicine, Sacramento, CA, USA
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Khalil WJ, Akeblersane M, Khan AS, Moin ASM, Butler AE. Environmental Pollution and the Risk of Developing Metabolic Disorders: Obesity and Diabetes. Int J Mol Sci 2023; 24:8870. [PMID: 37240215 PMCID: PMC10219141 DOI: 10.3390/ijms24108870] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 04/25/2023] [Accepted: 05/13/2023] [Indexed: 05/28/2023] Open
Abstract
To meet the increased need for food and energy because of the economic shift brought about by the Industrial Revolution in the 19th century, there has been an increase in persistent organic pollutants (POPs), atmospheric emissions and metals in the environment. Several studies have reported a relationship between these pollutants and obesity, and diabetes (type 1, type 2 and gestational). All of the major pollutants are considered to be endocrine disruptors because of their interactions with various transcription factors, receptors and tissues that result in alterations of metabolic function. POPs impact adipogenesis, thereby increasing the prevalence of obesity in exposed individuals. Metals impact glucose regulation by disrupting pancreatic β-cells, causing hyperglycemia and impaired insulin signaling. Additionally, a positive association has been observed between the concentration of endocrine disrupting chemicals (EDCs) in the 12 weeks prior to conception and fasting glucose levels. Here, we evaluate what is currently known regarding the link between environmental pollutants and metabolic disorders. In addition, we indicate where further research is required to improve our understanding of the specific effects of pollutants on these metabolic disorders which would enable implementation of changes to enable their prevention.
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Affiliation(s)
- William Junior Khalil
- School of Medicine, Royal College of Surgeons in Ireland Bahrain, Busaiteen 15503, Bahrain
| | - Meriem Akeblersane
- School of Medicine, Royal College of Surgeons in Ireland Bahrain, Busaiteen 15503, Bahrain
| | - Ana Saad Khan
- School of Medicine, Royal College of Surgeons in Ireland Bahrain, Busaiteen 15503, Bahrain
| | - Abu Saleh Md Moin
- Research Department, Royal College of Surgeons in Ireland Bahrain, Busaiteen 15503, Bahrain
| | - Alexandra E. Butler
- Research Department, Royal College of Surgeons in Ireland Bahrain, Busaiteen 15503, Bahrain
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Elbeltagi R, Al-Beltagi M, Saeed NK, Bediwy AS. Cardiometabolic effects of breastfeeding on infants of diabetic mothers. World J Diabetes 2023; 14:617-631. [PMID: 37273257 PMCID: PMC10236993 DOI: 10.4239/wjd.v14.i5.617] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 03/01/2023] [Accepted: 04/07/2023] [Indexed: 05/15/2023] Open
Abstract
BACKGROUND Breast milk is the best and principal nutritional source for neonates and infants. It may protect infants against many metabolic diseases, predominantly obesity and type 2 diabetes. Diabetes mellitus (DM) is a chronic metabolic and microvascular disease that affects all the body systems and all ages from intrauterine life to late adulthood. Breastfeeding protects against infant mortality and diseases, such as necrotizing enterocolitis, diarrhoea, respiratory infections, viral and bacterial infection, eczema, allergic rhinitis, asthma, food allergies, malocclusion, dental caries, Crohn's disease, and ulcerative colitis. It also protects against obesity and insulin resistance and increases intelligence and mental development. Gestational diabetes has short and long-term impacts on infants of diabetic mothers (IDM). Breast milk composition changes in mothers with gestational diabetes. AIM To investigate the beneficial or detrimental effects of breastfeeding on the cardiometabolic health of IDM and their mothers. METHODS We performed a database search on different engines and a thorough literature review and included 121 research published in English between January 2000 and December 15, 2022, in this review. RESULTS Most of the literature agreed on the beneficial effects of breast milk for both the mother and the infant in the short and long terms. Breastfeeding protects mothers with gestational diabetes against obesity and type 2 DM. Despite some evidence of the protective effects of breastfeeding on IDM in the short and long term, the evidence is not strong enough due to the presence of many confounding factors and a lack of sufficient studies. CONCLUSION We need more comprehensive research to prove these effects. Despite many obstacles that may enface mothers with gestational diabetes to start and maintain breastfeeding, every effort should be made to encourage them to breastfeed.
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Affiliation(s)
- Reem Elbeltagi
- Department of Medicine, Irish Royal College of Surgeon, Busaiteen 15503, Bahrain
| | - Mohammed Al-Beltagi
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Egypt
- Department of Pediatrics, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
| | - Nermin Kamal Saeed
- Medical Microbiology Section, Department of Pathology, Salmaniya Medical Complex, Ministry of Health, Kingdom of Bahrain, Manama 12, Bahrain
- Department of Microbiology, Irish Royal College of Surgeon, Bahrain, Busaiteen 15503, Bahrain
| | - Adel Salah Bediwy
- Department of Chest Diseases, Faculty of Medicine, Tanta University, Tanta 31527, Egypt
- Department of Pulmonology, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
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Rossnerova A, Elzeinova F, Chvojkova I, Honkova K, Sima M, Milcova A, Pastorkova A, Schmuczerova J, Rossner P, Topinka J, Sram RJ. Effects of various environments on epigenetic settings and chromosomal damage. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2023; 323:121290. [PMID: 36804881 DOI: 10.1016/j.envpol.2023.121290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 02/10/2023] [Accepted: 02/12/2023] [Indexed: 06/18/2023]
Abstract
Air pollution is a dominant environmental exposure factor with significant health consequences. Unexpectedly, research in a heavily polluted region of the Czech Republic, with traditional heavy industry, revealed repeatedly the lowest frequency of micronuclei in the season with the highest concentrations of air pollutants including carcinogenic benzo[a]pyrene (B[a]P). Molecular findings have been collected for more than 10 years from various locations of the Czech Republic, with differing quality of ambient air. Preliminary conclusions have suggested adaptation of the population from the polluted locality (Ostrava, Moravian-Silesian Region (MSR)) to chronic air pollution exposure. In this study we utilize the previous findings and, for the first time, investigate micronuclei (MN) frequency by type: (i) centromere positive (CEN+) MN, representing chromosomal losses, and (ii) centromere negative (CEN-) MN representing chromosomal breaks. As previous results indicated differences between populations in the expression of XRCC5, a gene involved in the non-homologous end-joining (NHEJ) repair pathway, possible variations in epigenetic settings in this gene were also investigated. This new research was conducted in two seasons in the groups from two localities with different air quality levels (Ostrava (OS) and Prague (PG)). The obtained new results show significantly lower frequencies of chromosomal breaks in the OS subjects, related to the highest air pollution levels (p < 0.001). In contrast, chromosomal losses were comparable between both groups. In addition, significantly lower DNA methylation was found in 14.3% of the analyzed CpG loci of XRCC5 in the population from OS. In conclusion, the epigenetic adaptation (hypomethylation) in XRCC5 involved in the NHEJ repair pathway in the population from the polluted region, was suggested as a reason for the reduced level of chromosomal breaks. Further research is needed to explore the additional mechanisms, including genetic adaptation.
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Affiliation(s)
- Andrea Rossnerova
- Department of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine CAS, Videnska 1083, 142 20, Prague 4, Czech Republic; Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine CAS, Videnska 1083, 142 20, Prague 4, Czech Republic.
| | - Fatima Elzeinova
- Department of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine CAS, Videnska 1083, 142 20, Prague 4, Czech Republic.
| | - Irena Chvojkova
- Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine CAS, Videnska 1083, 142 20, Prague 4, Czech Republic.
| | - Katerina Honkova
- Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine CAS, Videnska 1083, 142 20, Prague 4, Czech Republic.
| | - Michal Sima
- Department of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine CAS, Videnska 1083, 142 20, Prague 4, Czech Republic.
| | - Alena Milcova
- Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine CAS, Videnska 1083, 142 20, Prague 4, Czech Republic.
| | - Anna Pastorkova
- Department of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine CAS, Videnska 1083, 142 20, Prague 4, Czech Republic.
| | - Jana Schmuczerova
- Department of Medical Genetics, L. Pasteur University Hospital, Trieda SNP 1, 040 11, Kosice, Slovakia.
| | - Pavel Rossner
- Department of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine CAS, Videnska 1083, 142 20, Prague 4, Czech Republic.
| | - Jan Topinka
- Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine CAS, Videnska 1083, 142 20, Prague 4, Czech Republic.
| | - Radim J Sram
- Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine CAS, Videnska 1083, 142 20, Prague 4, Czech Republic.
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Poursafa P, Kamali Z, Fraszczyk E, Boezen HM, Vaez A, Snieder H. DNA methylation: a potential mediator between air pollution and metabolic syndrome. Clin Epigenetics 2022; 14:82. [PMID: 35773726 PMCID: PMC9245491 DOI: 10.1186/s13148-022-01301-y] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 06/01/2022] [Indexed: 01/19/2023] Open
Abstract
Given the global increase in air pollution and its crucial role in human health, as well as the steep rise in prevalence of metabolic syndrome (MetS), a better understanding of the underlying mechanisms by which environmental pollution may influence MetS is imperative. Exposure to air pollution is known to impact DNA methylation, which in turn may affect human health. This paper comprehensively reviews the evidence for the hypothesis that the effect of air pollution on the MetS is mediated by DNA methylation in blood. First, we present a summary of the impact of air pollution on metabolic dysregulation, including the components of MetS, i.e., disorders in blood glucose, lipid profile, blood pressure, and obesity. Then, we provide evidence on the relation between air pollution and endothelial dysfunction as one possible mechanism underlying the relation between air pollution and MetS. Subsequently, we review the evidence that air pollution (PM, ozone, NO2 and PAHs) influences DNA methylation. Finally, we summarize association studies between DNA methylation and MetS. Integration of current evidence supports our hypothesis that methylation may partly mediate the effect of air pollution on MetS.
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Affiliation(s)
- Parinaz Poursafa
- Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Zoha Kamali
- Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- Department of Bioinformatics, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Eliza Fraszczyk
- Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - H Marike Boezen
- Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Ahmad Vaez
- Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
- Department of Bioinformatics, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Harold Snieder
- Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
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Hatmal MM, Al-Hatamleh MAI, Olaimat AN, Alshaer W, Hasan H, Albakri KA, Alkhafaji E, Issa NN, Al-Holy MA, Abderrahman SM, Abdallah AM, Mohamud R. Immunomodulatory Properties of Human Breast Milk: MicroRNA Contents and Potential Epigenetic Effects. Biomedicines 2022; 10:1219. [PMID: 35740242 PMCID: PMC9219990 DOI: 10.3390/biomedicines10061219] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Revised: 05/15/2022] [Accepted: 05/17/2022] [Indexed: 02/07/2023] Open
Abstract
Infants who are exclusively breastfed in the first six months of age receive adequate nutrients, achieving optimal immune protection and growth. In addition to the known nutritional components of human breast milk (HBM), i.e., water, carbohydrates, fats and proteins, it is also a rich source of microRNAs, which impact epigenetic mechanisms. This comprehensive work presents an up-to-date overview of the immunomodulatory constituents of HBM, highlighting its content of circulating microRNAs. The epigenetic effects of HBM are discussed, especially those regulated by miRNAs. HBM contains more than 1400 microRNAs. The majority of these microRNAs originate from the lactating gland and are based on the remodeling of cells in the gland during breastfeeding. These miRNAs can affect epigenetic patterns by several mechanisms, including DNA methylation, histone modifications and RNA regulation, which could ultimately result in alterations in gene expressions. Therefore, the unique microRNA profile of HBM, including exosomal microRNAs, is implicated in the regulation of the genes responsible for a variety of immunological and physiological functions, such as FTO, INS, IGF1, NRF2, GLUT1 and FOXP3 genes. Hence, studying the HBM miRNA composition is important for improving the nutritional approaches for pregnancy and infant's early life and preventing diseases that could occur in the future. Interestingly, the composition of miRNAs in HBM is affected by multiple factors, including diet, environmental and genetic factors.
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Affiliation(s)
- Ma’mon M. Hatmal
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan;
| | - Mohammad A. I. Al-Hatamleh
- Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kota Bharu 16150, Malaysia;
| | - Amin N. Olaimat
- Department of Clinical Nutrition and Dietetics, Faculty of Applied Medical Sciences, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan; (A.N.O.); (M.A.A.-H.)
| | - Walhan Alshaer
- Cell Therapy Center (CTC), The University of Jordan, Amman 11942, Jordan;
| | - Hanan Hasan
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan;
| | - Khaled A. Albakri
- Faculty of Medicine, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan;
| | - Enas Alkhafaji
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan, Amman 11942, Jordan;
| | - Nada N. Issa
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan;
| | - Murad A. Al-Holy
- Department of Clinical Nutrition and Dietetics, Faculty of Applied Medical Sciences, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan; (A.N.O.); (M.A.A.-H.)
| | - Salim M. Abderrahman
- Department of Biology and Biotechnology, Faculty of Sciences, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan;
| | - Atiyeh M. Abdallah
- Department of Biomedical Sciences, College of Health Sciences, QU Health, Qatar University, Doha 2713, Qatar;
| | - Rohimah Mohamud
- Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kota Bharu 16150, Malaysia;
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Honkova K, Rossnerova A, Chvojkova I, Milcova A, Margaryan H, Pastorkova A, Ambroz A, Rossner P, Jirik V, Rubes J, Sram RJ, Topinka J. Genome-Wide DNA Methylation in Policemen Working in Cities Differing by Major Sources of Air Pollution. Int J Mol Sci 2022; 23:ijms23031666. [PMID: 35163587 PMCID: PMC8915177 DOI: 10.3390/ijms23031666] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Revised: 01/27/2022] [Accepted: 01/28/2022] [Indexed: 02/04/2023] Open
Abstract
DNA methylation is the most studied epigenetic mechanism that regulates gene expression, and it can serve as a useful biomarker of prior environmental exposure and future health outcomes. This study focused on DNA methylation profiles in a human cohort, comprising 125 nonsmoking city policemen (sampled twice), living and working in three localities (Prague, Ostrava and Ceske Budejovice) of the Czech Republic, who spent the majority of their working time outdoors. The main characterization of the localities, differing by major sources of air pollution, was defined by the stationary air pollution monitoring of PM2.5, B[a]P and NO2. DNA methylation was analyzed by a genome-wide microarray method. No season-specific DNA methylation pattern was discovered; however, we identified 13,643 differentially methylated CpG loci (DML) for a comparison between the Prague and Ostrava groups. The most significant DML was cg10123377 (log2FC = −1.92, p = 8.30 × 10−4) and loci annotated to RPTOR (total 20 CpG loci). We also found two hypomethylated loci annotated to the DNA repair gene XRCC5. Groups of DML annotated to the same gene were linked to diabetes mellitus (KCNQ1), respiratory diseases (PTPRN2), the dopaminergic system of the brain and neurodegenerative diseases (NR4A2). The most significant possibly affected pathway was Axon guidance, with 86 potentially deregulated genes near DML. The cluster of gene sets that could be affected by DNA methylation in the Ostrava groups mainly includes the neuronal functions and biological processes of cell junctions and adhesion assembly. The study demonstrates that the differences in the type of air pollution between localities can affect a unique change in DNA methylation profiles across the human genome.
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Affiliation(s)
- Katerina Honkova
- Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague 4, Czech Republic; (A.R.); (I.C.); (A.M.); (H.M.); (R.J.S.); (J.T.)
- Correspondence: ; Tel.: +420-775-406-170
| | - Andrea Rossnerova
- Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague 4, Czech Republic; (A.R.); (I.C.); (A.M.); (H.M.); (R.J.S.); (J.T.)
| | - Irena Chvojkova
- Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague 4, Czech Republic; (A.R.); (I.C.); (A.M.); (H.M.); (R.J.S.); (J.T.)
| | - Alena Milcova
- Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague 4, Czech Republic; (A.R.); (I.C.); (A.M.); (H.M.); (R.J.S.); (J.T.)
| | - Hasmik Margaryan
- Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague 4, Czech Republic; (A.R.); (I.C.); (A.M.); (H.M.); (R.J.S.); (J.T.)
| | - Anna Pastorkova
- Department of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague 4, Czech Republic; (A.P.); (A.A.); (P.R.J.)
| | - Antonin Ambroz
- Department of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague 4, Czech Republic; (A.P.); (A.A.); (P.R.J.)
| | - Pavel Rossner
- Department of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague 4, Czech Republic; (A.P.); (A.A.); (P.R.J.)
| | - Vitezslav Jirik
- Centre for Epidemiological Research, Faculty of Medicine, University of Ostrava, Syllabova 19, 703 00 Ostrava, Czech Republic;
| | - Jiri Rubes
- Veterinary Research Institute, Hudcova 296/70, 621 00 Brno, Czech Republic;
| | - Radim J. Sram
- Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague 4, Czech Republic; (A.R.); (I.C.); (A.M.); (H.M.); (R.J.S.); (J.T.)
| | - Jan Topinka
- Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague 4, Czech Republic; (A.R.); (I.C.); (A.M.); (H.M.); (R.J.S.); (J.T.)
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Guo C, Lv S, Liu Y, Li Y. Biomarkers for the adverse effects on respiratory system health associated with atmospheric particulate matter exposure. JOURNAL OF HAZARDOUS MATERIALS 2022; 421:126760. [PMID: 34396970 DOI: 10.1016/j.jhazmat.2021.126760] [Citation(s) in RCA: 66] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 07/17/2021] [Accepted: 07/25/2021] [Indexed: 06/13/2023]
Abstract
Large amounts of epidemiological evidence have confirmed the atmospheric particulate matter (PM2.5) exposure was positively correlated with the morbidity and mortality of respiratory diseases. Nevertheless, its pathogenesis remains incompletely understood, probably resulting from the activation of oxidative stress, inflammation, altered genetic and epigenetic modifications in the lung upon PM2.5 exposure. Currently, biomarker investigations have been widely used in epidemiological and toxicological studies, which may help in understanding the biologic mechanisms underlying PM2.5-elicited adverse health outcomes. Here, the emerging biomarkers to indicate PM2.5-respiratory system interactions were summarized, primarily related to oxidative stress (ROS, MDA, GSH, etc.), inflammation (Interleukins, FENO, CC16, etc.), DNA damage (8-OHdG, γH2AX, OGG1) and also epigenetic modulation (DNA methylation, histone modification, microRNAs). The identified biomarkers shed light on PM2.5-elicited inflammation, fibrogenesis and carcinogenesis, thus may favor more precise interventions in public health. It is worth noting that some inconsistent findings may possibly relate to the inter-study differentials in the airborne PM2.5 sample, exposure mode and targeted subjects, as well as methodological issues. Further research, particularly by -omics technique to identify novel, specific biomarkers, is warranted to illuminate the causal relationship between PM2.5 pollution and deleterious lung outcomes.
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Affiliation(s)
- Caixia Guo
- Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China
| | - Songqing Lv
- Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China; Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, China
| | - Yufan Liu
- Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China; Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, China
| | - Yanbo Li
- Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China; Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, China.
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Yadav S, Longkumer I, Garg PR, Joshi S, Rajkumari S, Devi NK, Saraswathy KN. Association of air pollution and homocysteine with global DNA methylation: A population-based study from North India. PLoS One 2021; 16:e0260860. [PMID: 34855899 PMCID: PMC8638980 DOI: 10.1371/journal.pone.0260860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Accepted: 11/17/2021] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Anthropogenic air pollution has been implicated in aberrant changes of DNA methylation and homocysteine increase (>15μM/L). Folate (<3 ng/mL) and vitamin B12 (<220 pg/mL) deficiencies also reduce global DNA methylation via homocysteine increase. Although B-vitamin supplements can attenuate epigenetic effects of air pollution but such understanding in population-specific studies are lacking. Hence, the present study aims to understand the role of air pollution, homocysteine, and nutritional deficiencies on methylation. METHODS We examined cross-sectionally, homocysteine, folate, vitamin B12 (chemiluminescence) and global DNA methylation (colorimetric ELISA Assay) among 274 and 270 individuals from low- and high- polluted areas, respectively, from a single Mendelian population. Global DNA methylation results were obtained on 254 and 258 samples from low- and high- polluted areas, respectively. RESULTS Significant decline in median global DNA methylation was seen as a result of air pollution [high-0.84 (0.37-1.97) vs. low-0.96 (0.45-2.75), p = 0.01]. High homocysteine in combination with air pollution significantly reduced global DNA methylation [high-0.71 (0.34-1.90) vs. low-0.93 (0.45-3.00), p = 0.003]. Folate deficient individuals in high polluted areas [high-0.70 (0.37-1.29) vs. low-1.21 (0.45-3.65)] showed significantly reduced global methylation levels (p = 0.007). In low polluted areas, despite folate deficiency, if normal vitamin B12 levels were maintained, global DNA methylation levels improved significantly [2.03 (0.60-5.24), p = 0.007]. Conversely, in high polluted areas despite vitamin B12 deficiency, if normal folate status was maintained, global DNA methylation status improved significantly [0.91 (0.36-1.63)] compared to vitamin B12 normal individuals [0.54 (0.26-1.13), p = 0.04]. CONCLUSIONS High homocysteine may aggravate the effects of air pollution on DNA methylation. Vitamin B12 in low-polluted and folate in high-polluted areas may be strong determinants for changes in DNA methylation levels. The effect of air pollution on methylation levels may be reduced through inclusion of dietary or supplemented B-vitamins. This may serve as public level approach in natural settings to prevent metabolic adversities at community level.
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Affiliation(s)
- Suniti Yadav
- Laboratory of Biochemical and Molecular Anthropology, Department of Anthropology, University of Delhi, Delhi, India
| | - Imnameren Longkumer
- Laboratory of Biochemical and Molecular Anthropology, Department of Anthropology, University of Delhi, Delhi, India
| | | | - Shipra Joshi
- Manbhum Ananda Ashram Nityananda Trust-MANT, Kolkata, West Bengal, India
| | - Sunanda Rajkumari
- Laboratory of Biochemical and Molecular Anthropology, Department of Anthropology, University of Delhi, Delhi, India
| | - Naorem Kiranmala Devi
- Laboratory of Biochemical and Molecular Anthropology, Department of Anthropology, University of Delhi, Delhi, India
| | - Kallur Nava Saraswathy
- Laboratory of Biochemical and Molecular Anthropology, Department of Anthropology, University of Delhi, Delhi, India
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11
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Rossnerova A, Honkova K, Chvojkova I, Pelclova D, Zdimal V, Hubacek JA, Lischkova L, Vlckova S, Ondracek J, Dvorackova S, Topinka J, Rossner P. Individual DNA Methylation Pattern Shifts in Nanoparticles-Exposed Workers Analyzed in Four Consecutive Years. Int J Mol Sci 2021; 22:ijms22157834. [PMID: 34360600 PMCID: PMC8346047 DOI: 10.3390/ijms22157834] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Revised: 07/15/2021] [Accepted: 07/21/2021] [Indexed: 12/21/2022] Open
Abstract
A DNA methylation pattern represents an original plan of the function settings of individual cells and tissues. The basic strategies of its development and changes during the human lifetime are known, but the details related to its modification over the years on an individual basis have not yet been studied. Moreover, current evidence shows that environmental exposure could generate changes in DNA methylation settings and, subsequently, the function of genes. In this study, we analyzed the effect of chronic exposure to nanoparticles (NP) in occupationally exposed workers repeatedly sampled in four consecutive years (2016-2019). A detailed methylation pattern analysis of 14 persons (10 exposed and 4 controls) was performed on an individual basis. A microarray-based approach using chips, allowing the assessment of more than 850 K CpG loci, was used. Individual DNA methylation patterns were compared by principal component analysis (PCA). The results show the shift in DNA methylation patterns in individual years in all the exposed and control subjects. The overall range of differences varied between the years in individual persons. The differences between the first and last year of examination (a three-year time period) seem to be consistently greater in the NP-exposed subjects in comparison with the controls. The selected 14 most differently methylated cg loci were relatively stable in the chronically exposed subjects. In summary, the specific type of long-term exposure can contribute to the fixing of relevant epigenetic changes related to a specific environment as, e.g., NP inhalation.
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Affiliation(s)
- Andrea Rossnerova
- Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague 4, Czech Republic; (K.H.); (I.C.); (J.T.)
- Correspondence: ; Tel.: +420-241-062-053
| | - Katerina Honkova
- Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague 4, Czech Republic; (K.H.); (I.C.); (J.T.)
| | - Irena Chvojkova
- Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague 4, Czech Republic; (K.H.); (I.C.); (J.T.)
| | - Daniela Pelclova
- Department of Occupational Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Na Bojisti 1, 120 00 Prague 2, Czech Republic; (D.P.); (L.L.); (S.V.)
| | - Vladimir Zdimal
- Department of Aerosol Chemistry and Physics, Institute of Chemical Process Fundamentals CAS, Rozvojova 1, 165 02 Prague 6, Czech Republic; (V.Z.); (J.O.)
| | - Jaroslav A. Hubacek
- Experimental Medicine Centre, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 140 21 Prague 4, Czech Republic;
| | - Lucie Lischkova
- Department of Occupational Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Na Bojisti 1, 120 00 Prague 2, Czech Republic; (D.P.); (L.L.); (S.V.)
| | - Stepanka Vlckova
- Department of Occupational Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Na Bojisti 1, 120 00 Prague 2, Czech Republic; (D.P.); (L.L.); (S.V.)
| | - Jakub Ondracek
- Department of Aerosol Chemistry and Physics, Institute of Chemical Process Fundamentals CAS, Rozvojova 1, 165 02 Prague 6, Czech Republic; (V.Z.); (J.O.)
| | - Stepanka Dvorackova
- Department of Machining and Assembly, Department of Engineering Technology, Department of Material Science, Faculty of Mechanical Engineering, Technical University in Liberec, Studentska 1402/2, 461 17 Liberec, Czech Republic;
| | - Jan Topinka
- Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague 4, Czech Republic; (K.H.); (I.C.); (J.T.)
| | - Pavel Rossner
- Department of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague 4, Czech Republic;
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12
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Suhaimi NF, Jalaludin J, Abu Bakar S. Deoxyribonucleic acid (DNA) methylation in children exposed to air pollution: a possible mechanism underlying respiratory health effects development. REVIEWS ON ENVIRONMENTAL HEALTH 2021; 36:77-93. [PMID: 32857724 DOI: 10.1515/reveh-2020-0065] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Accepted: 07/13/2020] [Indexed: 06/11/2023]
Abstract
Air pollution is a substantial environmental threat to children and acts as acute and chronic disease risk factors alike. Several studies have previously evaluated epigenetic modifications concerning its exposure across various life stages. However, findings on epigenetic modifications as the consequences of air pollution during childhood are rather minimal. This review evaluated highly relevant studies in the field to analyze the existing literature regarding exposure to air pollution, with a focus on epigenetic alterations during childhood and their connections with respiratory health effects. The search was conducted using readily available electronic databases (PubMed and ScienceDirect) to screen for children's studies on epigenetic mechanisms following either pre- or post-natal exposure to air pollutants. Studies relevant enough and matched the predetermined criteria were chosen to be reviewed. Non-English articles and studies that did not report both air monitoring and epigenetic outcomes in the same article were excluded. The review found that epigenetic changes have been linked with exposure to air pollutants during early life with evidence and reports of how they may deregulate the epigenome balance, thus inducing disease progression in the future. Epigenetic studies evolve as a promising new approach in deciphering the underlying impacts of air pollution on deoxyribonucleic acid (DNA) due to links established between some of these epigenetic mechanisms and illnesses.
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Affiliation(s)
- Nur Faseeha Suhaimi
- Department of Environmental and Occupational Health, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
| | - Juliana Jalaludin
- Department of Environmental and Occupational Health, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
- Department of Occupational Health and Safety, Faculty of Public Health, Universitas Airlangga, 60115Surabaya, East Java, Indonesia
| | - Suhaili Abu Bakar
- Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
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13
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Mallisetty Y, Mukherjee N, Jiang Y, Chen S, Ewart S, Arshad SH, Holloway JW, Zhang H, Karmaus W. Epigenome-Wide Association of Infant Feeding and Changes in DNA Methylation from Birth to 10 Years. Nutrients 2020; 13:E99. [PMID: 33396735 PMCID: PMC7824231 DOI: 10.3390/nu13010099] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Revised: 12/21/2020] [Accepted: 12/28/2020] [Indexed: 02/07/2023] Open
Abstract
Epigenetic factors have been suggested as mediators of early-life nutrition to future health. Prior studies focused on breastfeeding effects on DNA methylation (DNAm), ignoring other feeding modes. In this analysis of the Isle of Wight birth cohort, feeding modes were categorized as exclusive breastfeeding (EBF), exclusive formula feeding (EFF), and mixed feeding based on whether the respective feeding mode lasted for at least 3 months. In addition, in the past, infant feeding modes were assessed using DNAm at one time point in childhood, not changes of DNAm. In this paper, methylation differences (delta DNAm) were calculated by subtracting residual methylation values at birth from age 10 years (adjusting for cell types and season of blood collection at both ages). These deltas were estimated for all methylation sites where cytosine was followed by guanine (cytosine guanine dinucleotide (CpG) sites). Then, we performed an epigenome-wide association study contrasting EBF, EFF, and mixed feeding with delta DNAm that represents changes in methylation from birth to 10 years. A total of 87 CpGs (EBF: 27 CpGs, EFF: 48 CpGs, mixed: 12 CpGs) were identified using separate linear regression models adjusting for confounders and multiple testing. The sum of all changes in methylation from birth to age 10 years was significantly lower in the EFF group. Correspondingly, the number of CpGs with a methylation decline was 4.7% higher reflecting 13,683 CpGs. Lower methylation related to exclusive formula feeding and its adverse potential for the child's development needs future research to reduce adverse health effects.
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Affiliation(s)
- Yamini Mallisetty
- Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis, Robison Hall, Memphis, TN 38152, USA; (Y.M.); (N.M.); (Y.J.); (H.Z.)
| | - Nandini Mukherjee
- Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis, Robison Hall, Memphis, TN 38152, USA; (Y.M.); (N.M.); (Y.J.); (H.Z.)
| | - Yu Jiang
- Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis, Robison Hall, Memphis, TN 38152, USA; (Y.M.); (N.M.); (Y.J.); (H.Z.)
| | - Su Chen
- Department of Mathematical Science, University of Memphis, Dunn Hall, Memphis, TN 38152, USA;
| | - Susan Ewart
- College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA;
| | - S. Hasan Arshad
- NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK; (S.H.A.); (J.W.H.)
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, UK
- The David Hide Asthma and Allergy Research Centre, St Mary’s Hospital, Isle of Wight PO30 5TG, UK
| | - John W. Holloway
- NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK; (S.H.A.); (J.W.H.)
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK
| | - Hongmei Zhang
- Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis, Robison Hall, Memphis, TN 38152, USA; (Y.M.); (N.M.); (Y.J.); (H.Z.)
| | - Wilfried Karmaus
- Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis, Robison Hall, Memphis, TN 38152, USA; (Y.M.); (N.M.); (Y.J.); (H.Z.)
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14
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Rossnerova A, Izzotti A, Pulliero A, Bast A, Rattan SIS, Rossner P. The Molecular Mechanisms of Adaptive Response Related to Environmental Stress. Int J Mol Sci 2020; 21:ijms21197053. [PMID: 32992730 PMCID: PMC7582272 DOI: 10.3390/ijms21197053] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 09/13/2020] [Accepted: 09/22/2020] [Indexed: 12/13/2022] Open
Abstract
The exposure of living organisms to environmental stress triggers defensive responses resulting in the activation of protective processes. Whenever the exposure occurs at low doses, defensive effects overwhelm the adverse effects of the exposure; this adaptive situation is referred to as “hormesis”. Environmental, physical, and nutritional hormetins lead to the stimulation and strengthening of the maintenance and repair systems in cells and tissues. Exercise, heat, and irradiation are examples of physical hormetins, which activate heat shock-, DNA repair-, and anti-oxidative-stress responses. The health promoting effect of many bio-actives in fruits and vegetables can be seen as the effect of mildly toxic compounds triggering this adaptive stimulus. Numerous studies indicate that living organisms possess the ability to adapt to adverse environmental conditions, as exemplified by the fact that DNA damage and gene expression profiling in populations living in the environment with high levels of air pollution do not correspond to the concentrations of pollutants. The molecular mechanisms of the hormetic response include modulation of (a) transcription factor Nrf2 activating the synthesis of glutathione and the subsequent protection of the cell; (b) DNA methylation; and (c) microRNA. These findings provide evidence that hormesis is a toxicological event, occurring at low exposure doses to environmental stressors, having the benefit for the maintenance of a healthy status.
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Affiliation(s)
- Andrea Rossnerova
- Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine, 14220 Prague, Czech Republic;
| | - Alberto Izzotti
- Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy;
- IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
| | - Alessandra Pulliero
- Department of Health Science, University of Genoa, 16132 Genoa, Italy
- Correspondence:
| | - Aalt Bast
- Department of Pharmacology and Toxicology, Maastricht University, 6200 MD Maastricht, The Netherlands;
- Campus Venlo, Maastricht University, 5900 AA Venlo, The Netherlands
| | - S. I. S. Rattan
- Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus, Denmark;
| | - Pavel Rossner
- Department of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine, 14220 Prague, Czech Republic;
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15
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Sram RJ. Impact of Air Pollution on the Health of the Population in Parts of the Czech Republic. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:E6454. [PMID: 32899757 PMCID: PMC7558327 DOI: 10.3390/ijerph17186454] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 08/28/2020] [Accepted: 09/03/2020] [Indexed: 12/19/2022]
Abstract
Thirty years ago, Northern Bohemia in the Czech Republic was one of the most air polluted areas in Europe. After political changes, the Czech government put forward a research program to determine if air pollution is really affecting human health. This program, later called the "Teplice Program", was initiated in collaboration with scientists from the United States Environmental Protection Agency (US EPA). This cooperation made possible the use of methods on the contemporary level. The very high concentrations of sulphur dioxide (SO2), particulate matter of 10 micrometers or less (PM10), and polycyclic aromatic hydrocarbons (PAHs) present in the air showed, for the first time, the impact of air pollutants on the health of the population in mining districts: adverse pregnancy outcomes, the impact of air pollution on sperm morphology, learning disabilities in children, and respiratory morbidity in preschool children. A surprising result came from the distribution of the sources of pollution: 70% of PM10 pollution came from local heating and not from power plants as expected. Thanks to this result, the Czech government supported changes in local heating from brown coal to natural gas. This change substantially decreased SO2 and PM10 pollution and affected mortality, especially cardiovascular mortality.
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Affiliation(s)
- Radim J Sram
- Faculty of Health and Social Science, University of South Bohemia, 370 05 Ceske Budejovice, Czech Republic
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16
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Sherwood WB, Kothalawala DM, Kadalayil L, Ewart S, Zhang H, Karmaus W, Arshad SH, Holloway JW, Rezwan FI. Epigenome-Wide Association Study Reveals Duration of Breastfeeding Is Associated with Epigenetic Differences in Children. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:E3569. [PMID: 32443666 PMCID: PMC7277240 DOI: 10.3390/ijerph17103569] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 05/15/2020] [Accepted: 05/17/2020] [Indexed: 12/21/2022]
Abstract
Several small studies have shown associations between breastfeeding and genome-wide DNA methylation (DNAm). We performed a comprehensive Epigenome-Wide Association Study (EWAS) to identify associations between breastfeeding and DNAm patterns in childhood. We analysed DNAm data from the Isle of Wight Birth Cohort at birth, 10, 18 and 26 years. The feeding method was categorized as breastfeeding duration >3 months and >6 months, and exclusive breastfeeding duration >3 months. EWASs using robust linear regression were performed to identify differentially methylated positions (DMPs) in breastfed and non-breastfed children at age 10 (false discovery rate of 5%). Differentially methylated regions (DMRs) were identified using comb-p. The persistence of significant associations was evaluated in neonates and individuals at 18 and 26 years. Two DMPs, in genes SNX25 and LINC00840, were significantly associated with breastfeeding duration >6 months at 10 years and was replicated for >3 months of exclusive breastfeeding. Additionally, a significant DMR spanning the gene FDFT1 was identified in 10-year-old children who were exposed to a breastfeeding duration >3 months. None of these signals persisted to 18 or 26 years. This study lends further support for a suggestive role of DNAm in the known benefits of breastfeeding on a child's future health.
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Affiliation(s)
- William B. Sherwood
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK; (W.B.S.); (D.M.K.); (L.K.); (F.I.R.)
| | - Dilini M. Kothalawala
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK; (W.B.S.); (D.M.K.); (L.K.); (F.I.R.)
- NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK;
| | - Latha Kadalayil
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK; (W.B.S.); (D.M.K.); (L.K.); (F.I.R.)
| | - Susan Ewart
- College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA;
| | - Hongmei Zhang
- Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis, 236A Robison Hall, Memphis, TN 38152, USA; (H.Z.); (W.K.)
| | - Wilfried Karmaus
- Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis, 236A Robison Hall, Memphis, TN 38152, USA; (H.Z.); (W.K.)
| | - S. Hasan Arshad
- NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK;
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK
- The David Hide Asthma and Allergy Research Centre, St Mary’s Hospital, Isle of Wight PO30 5TG UK
| | - John W. Holloway
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK; (W.B.S.); (D.M.K.); (L.K.); (F.I.R.)
- NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK;
| | - Faisal I. Rezwan
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK; (W.B.S.); (D.M.K.); (L.K.); (F.I.R.)
- School of Water, Energy and Environment, Cranfield University, Cranfield, Bedfordshire MK43 0AL, UK
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Xu J, Sram RJ, Cebulska-Wasilewska A, Miloradov MV, Sardas S, Au WW. Challenge-comet assay, a functional and genomic biomarker for precision risk assessment and disease prevention among exposed workers. Toxicol Appl Pharmacol 2020; 397:115011. [PMID: 32305282 DOI: 10.1016/j.taap.2020.115011] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Revised: 04/12/2020] [Accepted: 04/14/2020] [Indexed: 02/05/2023]
Abstract
Advancements in genomic technologies have ushered application of innovative changes into biomedical sciences and clinical medicine. Consequently, these changes have created enormous opportunities to implement precision population/occupational disease prevention and target-specific disease intervention (or personalized medicine). To capture the opportunities, however, it is necessary is to develop novel, especially genomic-based, biomarkers which can provide precise and individualized health risk assessment. In this review, development of the Challenge-comet assay is used as an example to demonstrate how assays need to be validated for its sensitivity, specificity, and functional and quantitative features, and how assays can be used to provide individualized health risk assessment for precision prevention and intervention. Other examples of genomic-based novel biomarkers will also be discussed. Furthermore, no biomarkers can be used alone therefore their integrated usage with other biomarkers and with personal data bases will be discussed.
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Affiliation(s)
- Jianzhen Xu
- Shantou University Medical College, Shantou, China
| | - Radim J Sram
- Institute of Experimental Medicine AS, CR, Prague, Czech Republic
| | | | | | - Semra Sardas
- Istinye University, Zeytinburnu, Istanbul, Turkey
| | - William W Au
- University of Medicine, Pharmacy, Sciences and Technology, Targu Mures, Romania; University of Texas Medical Branch, Galveston, TX, USA.
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18
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Rossnerova A, Honkova K, Pelclova D, Zdimal V, Hubacek JA, Chvojkova I, Vrbova K, Rossner P, Topinka J, Vlckova S, Fenclova Z, Lischkova L, Klusackova P, Schwarz J, Ondracek J, Ondrackova L, Kostejn M, Klema J, Dvorackova S. DNA Methylation Profiles in a Group of Workers Occupationally Exposed to Nanoparticles. Int J Mol Sci 2020; 21:E2420. [PMID: 32244494 PMCID: PMC7177382 DOI: 10.3390/ijms21072420] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Revised: 03/27/2020] [Accepted: 03/30/2020] [Indexed: 02/07/2023] Open
Abstract
The risk of exposure to nanoparticles (NPs) has rapidly increased during the last decade due to the vast use of nanomaterials (NMs) in many areas of human life. Despite this fact, human biomonitoring studies focused on the effect of NP exposure on DNA alterations are still rare. Furthermore, there are virtually no epigenetic data available. In this study, we investigated global and gene-specific DNA methylation profiles in a group of 20 long-term (mean 14.5 years) exposed, nanocomposite, research workers and in 20 controls. Both groups were sampled twice/day (pre-shift and post-shift) in September 2018. We applied Infinium Methylation Assay, using the Infinium MethylationEPIC BeadChips with more than 850,000 CpG loci, for identification of the DNA methylation pattern in the studied groups. Aerosol exposure monitoring, including two nanosized fractions, was also performed as proof of acute NP exposure. The obtained array data showed significant differences in methylation between the exposed and control groups related to long-term exposure, specifically 341 CpG loci were hypomethylated and 364 hypermethylated. The most significant CpG differences were mainly detected in genes involved in lipid metabolism, the immune system, lung functions, signaling pathways, cancer development and xenobiotic detoxification. In contrast, short-term acute NP exposure was not accompanied by DNA methylation changes. In summary, long-term (years) exposure to NP is associated with DNA epigenetic alterations.
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Affiliation(s)
- Andrea Rossnerova
- Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague 4, Czech Republic; (K.H.); (I.C.); (J.T.)
| | - Katerina Honkova
- Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague 4, Czech Republic; (K.H.); (I.C.); (J.T.)
| | - Daniela Pelclova
- Department of Occupational Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Na Bojisti 1, 120 00 Prague 2, Czech Republic; (D.P.); (S.V.); (Z.F.); (L.L.); (P.K.)
| | - Vladimir Zdimal
- Laboratory of Aerosol Chemistry and Physics, Institute of Chemical Process Fundamentals CAS, Rozvojova 1, 165 02 Prague 6, Czech Republic; (V.Z.); (J.S.); (J.O.); (L.O.); (M.K.)
| | - Jaroslav A. Hubacek
- Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 140 21 Prague 4, Czech Republic;
| | - Irena Chvojkova
- Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague 4, Czech Republic; (K.H.); (I.C.); (J.T.)
| | - Kristyna Vrbova
- Department of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague 4, Czech Republic; (K.V.); (P.R.)
| | - Pavel Rossner
- Department of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague 4, Czech Republic; (K.V.); (P.R.)
| | - Jan Topinka
- Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague 4, Czech Republic; (K.H.); (I.C.); (J.T.)
| | - Stepanka Vlckova
- Department of Occupational Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Na Bojisti 1, 120 00 Prague 2, Czech Republic; (D.P.); (S.V.); (Z.F.); (L.L.); (P.K.)
| | - Zdenka Fenclova
- Department of Occupational Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Na Bojisti 1, 120 00 Prague 2, Czech Republic; (D.P.); (S.V.); (Z.F.); (L.L.); (P.K.)
| | - Lucie Lischkova
- Department of Occupational Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Na Bojisti 1, 120 00 Prague 2, Czech Republic; (D.P.); (S.V.); (Z.F.); (L.L.); (P.K.)
| | - Pavlina Klusackova
- Department of Occupational Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Na Bojisti 1, 120 00 Prague 2, Czech Republic; (D.P.); (S.V.); (Z.F.); (L.L.); (P.K.)
| | - Jaroslav Schwarz
- Laboratory of Aerosol Chemistry and Physics, Institute of Chemical Process Fundamentals CAS, Rozvojova 1, 165 02 Prague 6, Czech Republic; (V.Z.); (J.S.); (J.O.); (L.O.); (M.K.)
| | - Jakub Ondracek
- Laboratory of Aerosol Chemistry and Physics, Institute of Chemical Process Fundamentals CAS, Rozvojova 1, 165 02 Prague 6, Czech Republic; (V.Z.); (J.S.); (J.O.); (L.O.); (M.K.)
| | - Lucie Ondrackova
- Laboratory of Aerosol Chemistry and Physics, Institute of Chemical Process Fundamentals CAS, Rozvojova 1, 165 02 Prague 6, Czech Republic; (V.Z.); (J.S.); (J.O.); (L.O.); (M.K.)
| | - Martin Kostejn
- Laboratory of Aerosol Chemistry and Physics, Institute of Chemical Process Fundamentals CAS, Rozvojova 1, 165 02 Prague 6, Czech Republic; (V.Z.); (J.S.); (J.O.); (L.O.); (M.K.)
| | - Jiri Klema
- Department of Computer Science, Czech Technical University in Prague, Karlovo namesti 13, 121 35 Prague 2, Czech Republic;
| | - Stepanka Dvorackova
- Department of Machining and Assembly, Department of Engineering Technology, Department of Material Science, Faculty of Mechanical Engineering, Technical University in Liberec, Studentska 1402/2 Liberec, Czech Republic;
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Odintsova VV, Hagenbeek FA, Suderman M, Caramaschi D, van Beijsterveldt CEM, Kallsen NA, Ehli EA, Davies GE, Sukhikh GT, Fanos V, Relton C, Bartels M, Boomsma DI, van Dongen J. DNA Methylation Signatures of Breastfeeding in Buccal Cells Collected in Mid-Childhood. Nutrients 2019; 11:E2804. [PMID: 31744183 PMCID: PMC6893543 DOI: 10.3390/nu11112804] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Revised: 11/12/2019] [Accepted: 11/12/2019] [Indexed: 12/11/2022] Open
Abstract
Breastfeeding has long-term benefits for children that may be mediated via the epigenome. This pathway has been hypothesized, but the number of empirical studies in humans is small and mostly done by using peripheral blood as the DNA source. We performed an epigenome-wide association study (EWAS) in buccal cells collected around age nine (mean = 9.5) from 1006 twins recruited by the Netherlands Twin Register (NTR). An age-stratified analysis examined if effects attenuate with age (median split at 10 years; n<10 = 517, mean age = 7.9; n>10 = 489, mean age = 11.2). We performed replication analyses in two independent cohorts from the NTR (buccal cells) and the Avon Longitudinal Study of Parents and Children (ALSPAC) (peripheral blood), and we tested loci previously associated with breastfeeding in epigenetic studies. Genome-wide DNA methylation was assessed with the Illumina Infinium MethylationEPIC BeadChip (Illumina, San Diego, CA, USA) in the NTR and with the HumanMethylation450 Bead Chip in the ALSPAC. The duration of breastfeeding was dichotomized ('never' vs. 'ever'). In the total sample, no robustly associated epigenome-wide significant CpGs were identified (α = 6.34 × 10-8). In the sub-group of children younger than 10 years, four significant CpGs were associated with breastfeeding after adjusting for child and maternal characteristics. In children older than 10 years, methylation differences at these CpGs were smaller and non-significant. The findings did not replicate in the NTR sample (n = 98; mean age = 7.5 years), and no nearby sites were associated with breastfeeding in the ALSPAC study (n = 938; mean age = 7.4). Of the CpG sites previously reported in the literature, three were associated with breastfeeding in children younger than 10 years, thus showing that these CpGs are associated with breastfeeding in buccal and blood cells. Our study is the first to show that breastfeeding is associated with epigenetic variation in buccal cells in children. Further studies are needed to investigate if methylation differences at these loci are caused by breastfeeding or by other unmeasured confounders, as well as what mechanism drives changes in associations with age.
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Affiliation(s)
- Veronika V. Odintsova
- Department of Biological Psychology, Vrije Universiteit Amsterdam, 1081 BT Amsterdam, The Netherlands (D.I.B.)
- Amsterdam Public Health Research Institute, 1081 BT Amsterdam, The Netherlands
- Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow 101000, Russia
| | - Fiona A. Hagenbeek
- Department of Biological Psychology, Vrije Universiteit Amsterdam, 1081 BT Amsterdam, The Netherlands (D.I.B.)
- Amsterdam Public Health Research Institute, 1081 BT Amsterdam, The Netherlands
| | - Matthew Suderman
- MRC Integrative Epidemiology Unit, Bristol Medical School, Population Health Science, University of Bristol, Bristol BS8 1TH, UK
| | - Doretta Caramaschi
- MRC Integrative Epidemiology Unit, Bristol Medical School, Population Health Science, University of Bristol, Bristol BS8 1TH, UK
| | | | - Noah A. Kallsen
- Avera Institute for Human Genetics, Sioux Falls, SD 57101, USA
| | - Erik A. Ehli
- Avera Institute for Human Genetics, Sioux Falls, SD 57101, USA
| | | | - Gennady T. Sukhikh
- Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow 101000, Russia
| | - Vassilios Fanos
- Neonatal Intensive Care Unit, Department of Surgical Sciences, AOU and University of Cagliari, 09121 Cagliari, Italy
| | - Caroline Relton
- MRC Integrative Epidemiology Unit, Bristol Medical School, Population Health Science, University of Bristol, Bristol BS8 1TH, UK
| | - Meike Bartels
- Department of Biological Psychology, Vrije Universiteit Amsterdam, 1081 BT Amsterdam, The Netherlands (D.I.B.)
- Amsterdam Public Health Research Institute, 1081 BT Amsterdam, The Netherlands
| | - Dorret I. Boomsma
- Department of Biological Psychology, Vrije Universiteit Amsterdam, 1081 BT Amsterdam, The Netherlands (D.I.B.)
- Amsterdam Public Health Research Institute, 1081 BT Amsterdam, The Netherlands
| | - Jenny van Dongen
- Department of Biological Psychology, Vrije Universiteit Amsterdam, 1081 BT Amsterdam, The Netherlands (D.I.B.)
- Amsterdam Public Health Research Institute, 1081 BT Amsterdam, The Netherlands
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20
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Zielinska MA, Hamulka J. Protective Effect of Breastfeeding on the Adverse Health Effects Induced by Air Pollution: Current Evidence and Possible Mechanisms. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:E4181. [PMID: 31671856 PMCID: PMC6862650 DOI: 10.3390/ijerph16214181] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/06/2019] [Revised: 10/22/2019] [Accepted: 10/25/2019] [Indexed: 02/08/2023]
Abstract
Air pollution is a major social, economic, and health problem around the world. Children are particularly susceptible to the negative effects of air pollution due to their immaturity and excessive growth and development. The aims of this narrative review were to: (1) summarize evidence about the protective effects of breastfeeding on the adverse health effects of air pollution exposure, (2) define and describe the potential mechanisms underlying the protective effects of breastfeeding, and (3) examine the potential effects of air pollution on breastmilk composition and lactation. A literature search was conducted using electronic databases. Existing evidence suggests that breastfeeding has a protective effect on adverse outcomes of indoor and outdoor air pollution exposure in respiratory (infections, lung function, asthma symptoms) and immune (allergic, nervous and cardiovascular) systems, as well as under-five mortality in both developing and developed countries. However, some studies reported no protective effect of breastfeeding or even negative effects of breastfeeding for under-five mortality. Several possible mechanisms of the breastfeeding protective effect were proposed, including the beneficial influence of breastfeeding on immune, respiratory, and nervous systems, which are related to the immunomodulatory, anti-inflammatory, anti-oxidant, and neuroprotective properties of breastmilk. Breastmilk components responsible for its protective effect against air pollutants exposure may be long chain polyunsaturated fatty acids (LC PUFA), antioxidant vitamins, carotenoids, flavonoids, immunoglobins, and cytokines, some of which have concentrations that are diet-dependent. However, maternal exposure to air pollution is related to increased breastmilk concentrations of pollutants (e.g., Polycyclic aromatic hydrocarbons (PAHs) or heavy metals in particulate matter (PM)). Nonetheless, environmental studies have confirmed that breastmilk's protective effects outweigh its potential health risk to the infant. Mothers should be encouraged and supported to breastfeed their infants due to its unique health benefits, as well as its limited ecological footprint, which is associated with decreased waste production and the emission of pollutants.
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Affiliation(s)
- Monika A Zielinska
- Department of Human Nutrition, Institute of Human Nutrition Sciences, Warsaw University of Life Sciences-SGGW, 159C Nowoursynowska Street, 02-776 Warsaw, Poland.
| | - Jadwiga Hamulka
- Department of Human Nutrition, Institute of Human Nutrition Sciences, Warsaw University of Life Sciences-SGGW, 159C Nowoursynowska Street, 02-776 Warsaw, Poland.
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21
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Ferrari L, Carugno M, Bollati V. Particulate matter exposure shapes DNA methylation through the lifespan. Clin Epigenetics 2019; 11:129. [PMID: 31470889 PMCID: PMC6717322 DOI: 10.1186/s13148-019-0726-x] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Accepted: 08/16/2019] [Indexed: 12/11/2022] Open
Abstract
Exposure to airborne particulate matter (PM) has been associated with detrimental health effects. DNA methylation represents the most well-studied epigenetic factor among the possible mechanisms underlying this association. Interestingly, changes of DNA methylation in response to environmental stimuli are being considered for their role in the pathogenic mechanism, but also as mediators of the body adaptation to air pollutants.Several studies have evaluated both global and gene-specific methylation in relation to PM exposure in different clinical conditions and life stages. The purpose of the present literature review is to evaluate the most relevant and recent studies in the field in order to analyze the available evidences on long- and short-term PM exposure and DNA methylation changes, with a particular focus on the different life stages when the alteration occurs. PM exposure modulates DNA methylation affecting several biological mechanisms with marked effects on health, especially during susceptible life stages such as pregnancy, childhood, and the older age.Although many cross-sectional investigations have been conducted so far, only a limited number of prospective studies have explored the potential role of DNA methylation. Future studies are needed in order to evaluate whether these changes might be reverted.
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Affiliation(s)
- L Ferrari
- EPIGET-Epidemiology, Epigenetics and Toxicology Lab, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, via San Barnaba 8, 20122, Milan, Italy
| | - M Carugno
- EPIGET-Epidemiology, Epigenetics and Toxicology Lab, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, via San Barnaba 8, 20122, Milan, Italy
| | - V Bollati
- EPIGET-Epidemiology, Epigenetics and Toxicology Lab, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, via San Barnaba 8, 20122, Milan, Italy.
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22
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Sherwood WB, Bion V, Lockett GA, Ziyab AH, Soto-Ramírez N, Mukherjee N, Kurukulaaratchy RJ, Ewart S, Zhang H, Arshad SH, Karmaus W, Holloway JW, Rezwan FI. Duration of breastfeeding is associated with leptin (LEP) DNA methylation profiles and BMI in 10-year-old children. Clin Epigenetics 2019; 11:128. [PMID: 31464656 PMCID: PMC6716837 DOI: 10.1186/s13148-019-0727-9] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Accepted: 08/16/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Breastfeeding is protective against many long-term diseases, yet the mechanisms involved are unknown. Leptin gene (LEP) is reported to be associated with body mass index (BMI). On the other hand, breastfeeding duration has been found to be associated with DNA methylation (DNAm) of the LEP gene. Therefore, epigenetic regulation of LEP may represent the mechanism underlying the protective effect of breastfeeding duration against obesity. METHODS In the Isle of Wight Birth Cohort, peripheral blood DNAm at 23 cytosine-phosphate-guanine sites (CpGs) in the LEP locus in 10-year-old (n = 297) samples and 16 CpGs in 18-year-old (n = 305) samples, were generated using the Illumina Infinium MethylationEPIC and HumanMethylation450 Beadchips respectively and tested for association with breastfeeding duration (total and exclusive) using linear regression. To explore the association between breastfeeding durations and genome-wide DNAm, epigenome-wide association studies (EWASs) and differential methylation region (DMR) analyses were performed. BMI trajectories spanning the first 18 years of life were used as the outcome to test the association with breastfeeding duration (exposure) using multi-nominal logistic regression. Mediation analysis was performed for significant CpG sites. RESULTS Both total and exclusive breastfeeding duration were associated with DNAm at four LEP CpG sites at 10 years (P value < 0.05), and not at 18 years. Though no association was observed between breastfeeding duration and genome-wide DNAm, DMR analyses identified five significant differentially methylated regions (Sidak adjusted P value < 0.05). Breastfeeding duration was also associated with the early transient overweight trajectory. Furthermore, DNAm of LEP was associated with this trajectory at one CpG site and early persistent obesity at another, though mediation analysis was not significant. CONCLUSIONS Breastfeeding duration is associated with LEP methylation at age 10 years and BMI trajectory. LEP DNAm is also significantly associated with BMI trajectories throughout childhood, though sample sizes were small. However, mediation analysis did not demonstrate that DNAm of LEP explained the protective effect of breastfeeding against childhood obesity.
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Affiliation(s)
- William B Sherwood
- Human Development and Health, Faculty of Medicine, University Hospital Southampton, University of Southampton, Duthie Building, MP808, Tremona Road, Southampton, Hampshire, SO16 6YD, UK
| | - Victoria Bion
- Human Development and Health, Faculty of Medicine, University Hospital Southampton, University of Southampton, Duthie Building, MP808, Tremona Road, Southampton, Hampshire, SO16 6YD, UK
| | - Gabrielle A Lockett
- Human Development and Health, Faculty of Medicine, University Hospital Southampton, University of Southampton, Duthie Building, MP808, Tremona Road, Southampton, Hampshire, SO16 6YD, UK
| | - Ali H Ziyab
- Department of Community Medicine and Behavioral Sciences, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait
| | | | - Nandini Mukherjee
- Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis, 236A Robison Hall, Memphis, TN, 38152, USA
| | - Ramesh J Kurukulaaratchy
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
- The David Hide Asthma and Allergy Research Centre, Isle of Wight, UK
| | - Susan Ewart
- College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA
| | - Hongmei Zhang
- Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis, 236A Robison Hall, Memphis, TN, 38152, USA
| | - S Hasan Arshad
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
- The David Hide Asthma and Allergy Research Centre, Isle of Wight, UK
| | - Wilfried Karmaus
- Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis, 236A Robison Hall, Memphis, TN, 38152, USA
| | - John W Holloway
- Human Development and Health, Faculty of Medicine, University Hospital Southampton, University of Southampton, Duthie Building, MP808, Tremona Road, Southampton, Hampshire, SO16 6YD, UK
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Faisal I Rezwan
- Human Development and Health, Faculty of Medicine, University Hospital Southampton, University of Southampton, Duthie Building, MP808, Tremona Road, Southampton, Hampshire, SO16 6YD, UK.
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23
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Naumova OY, Odintsova VV, Arincina IA, Rychkov SY, Muhamedrahimov RJ, Shneider YV, Grosheva AN, Zhukova OV, Grigorenko EL. A Study of the Association between Breastfeeding and DNA Methylation in Peripheral Blood Cells of Infants. RUSS J GENET+ 2019. [DOI: 10.1134/s1022795419060103] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Choi H, Song WM, Wang M, Sram RJ, Zhang B. Benzo[a]pyrene is associated with dysregulated myelo-lymphoid hematopoiesis in asthmatic children. ENVIRONMENT INTERNATIONAL 2019; 128:218-232. [PMID: 31059917 DOI: 10.1016/j.envint.2019.04.052] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Revised: 04/21/2019] [Accepted: 04/22/2019] [Indexed: 06/09/2023]
Abstract
BACKGROUND The extent to which ambient benzo[a]pyrene (B[a]P) contributes to mechanistically distinct de novo asthma remains unknown. OBJECTIVES To identify molecular signatures and regulatory networks underlying childhood exposure to ambient B[a]P and asthma, using robust and unbiased systems biology approaches. METHODS Clinically confirmed asthmatic (n = 191) vs. control (n = 194) children (aged, 7-15) were enrolled from a polluted urban center and semi-rural region in Czech Republic. Contemporaneous B[a]P concentration, gene expressions, DNA methylation data were analyzed against asthma diagnosis, as well as a modified prognostic index of asthma, using integrative multiscale co-expression network analysis. Sample-wise cell type compositions were inferred by a machine learning approach (i.e. CIBERSORT) with reference gene expressions of purified 38 distinct hematopoietic cell states from umbilical cord (i.e. stem cell/progenitors) or peripheral blood (i.e. lymphocytes). RESULTS The median outdoor B[a]P was increased near the homes of the urban children with 'moderate' or 'severe' prognostic markers of asthma, but not in the urban controls. An elevated B[a]P induced epigenetic suppression of NF-κB inflammation, decreased Natural Killer T (NKT) cells and activated anti-inflammatory IL10-secreting CD8+ T effective memory cells. B[a]P was positively correlated with an increased expression of a heme biosynthesis gene, ALAS2, which in turn, appears to promote concurrent increase of neutrophilic metamyelocyte and mature CD71low erythroid cells. Furthermore, erythroid-specific master transcription regulator gene (GATA1), glutathione transferase genes (GSTM1 and GSTM3) and Eosinophil marker (IL5RA) were simultaneously activated in the urban asthma cases. CONCLUSIONS B[a]P might contribute to concurrent suppression of pro-inflammatory (e.g. NF-κB mediated NKT cells), and activation of anti-inflammatory pathways (e.g. IL10-secreting CD8+ T cells) in the urban asthmatic children. In addition, B[a]P appears to elevate heme biosynthesis, which in turn, promotes neutrophilic metamyelocyte expansion and reduction of CD71+ erythroids.
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Affiliation(s)
- Hyunok Choi
- Departments of Environmental Health Sciences, Epidemiology, and Biostatistics, State University of New York at Albany School of Public Health, Rensselaer, NY, USA.
| | - Won-Min Song
- Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Minghui Wang
- Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Radim J Sram
- Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, v.v.i., Vídeňská 1083, 142 20 Prague 4, Czech Republic; University of Chemistry and Technology, Prague, Faculty of Food and Biochemical Technology, Department of Food Analysis and Nutrition, Technicka 3, 166 28 Prague, Czech Republic
| | - Bin Zhang
- Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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Alfano R, Herceg Z, Nawrot TS, Chadeau-Hyam M, Ghantous A, Plusquin M. The Impact of Air Pollution on Our Epigenome: How Far Is the Evidence? (A Systematic Review). Curr Environ Health Rep 2018; 5:544-578. [PMID: 30361985 DOI: 10.1007/s40572-018-0218-8] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
PURPOSE OF REVIEW This systematic review evaluated existing evidence linking air pollution exposure in humans to major epigenetic mechanisms: DNA methylation, microRNAs, long noncoding RNAs, and chromatin regulation. RECENT FINDINGS Eighty-two manuscripts were eligible, most of which were observational (85%), conducted in adults (66%) and based on DNA methylation (79%). Most observational studies, except panel, demonstrated modest effects of air pollution on the methylome. Panel and experimental studies revealed a relatively large number of significant methylome alterations, though based on smaller sample sizes. Particulate matter levels were positively associated in several studies with global or LINE-1 hypomethylation, a hallmark of several diseases, and with decondensed chromatin structure. Several air pollution species altered the DNA methylation clock, inducing accelerated biological aging. The causal nature of identified associations is not clear, however, especially that most originate from countries with low air pollution levels. Existing evidence, gaps, and perspectives are highlighted herein.
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Affiliation(s)
- Rossella Alfano
- Centre for Environmental Sciences, Hasselt University, Hasselt, Belgium
| | - Zdenko Herceg
- Epigenetics Group, International Agency for Research on Cancer (IARC), 150 Cours Albert-Thomas, 69008, Lyon, France
| | - Tim S Nawrot
- Centre for Environmental Sciences, Hasselt University, Hasselt, Belgium
- Environment & Health Unit, Leuven University, Leuven, Belgium
| | - Marc Chadeau-Hyam
- Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, UK
| | - Akram Ghantous
- Epigenetics Group, International Agency for Research on Cancer (IARC), 150 Cours Albert-Thomas, 69008, Lyon, France.
| | - Michelle Plusquin
- Centre for Environmental Sciences, Hasselt University, Hasselt, Belgium.
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26
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Maddock J, Wulaningsih W, Fernandez JC, Ploubidis GB, Goodman A, Bell J, Kuh D, Hardy R. Associations between body size, nutrition and socioeconomic position in early life and the epigenome: A systematic review. PLoS One 2018; 13:e0201672. [PMID: 30096154 PMCID: PMC6086410 DOI: 10.1371/journal.pone.0201672] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Accepted: 07/18/2018] [Indexed: 12/19/2022] Open
Abstract
Background Body size, nutrition and socioeconomic position (SEP) in early life have been associated with a wide range of long-term health effects. Epigenetics is one possible mechanism through which these early life exposures can impact later life health. We conducted a systematic review examining the observational evidence for the impact of body size, nutrition and SEP in early life on the epigenome in humans. Methods This systematic review is registered with the PROSPERO database (registration number: CRD42016050193). Three datasets were simultaneously searched using Ovid and the resulting studies were evaluated by at least two independent reviewers. Studies measuring epigenetic markers either at the same time as, or after, the early life exposure and have a measure of body size, nutrition or SEP in early life (up to 12 years), written in English and from a community-dwelling participants were included. Results We identified 90 eligible studies. Seventeen of these papers examined more than one early life exposure of interest. Fifty six papers examined body size, 37 nutrition and 17 SEP. All of the included papers examined DNA methylation (DNAm) as the epigenetic marker. Overall there was no strong evidence for a consistent association between these early life variables in DNAm which may be due to the heterogeneous study designs, data collection methods and statistical analyses. Conclusions Despite these inconclusive results, the hypothesis that the early life environment can impact DNAm, potentially persisting into adult life, was supported by some studies and warrants further investigation. We provide recommendations for future studies.
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Affiliation(s)
- Jane Maddock
- MRC Unit for Lifelong Health and Ageing, Institute of Cardiovascular Science, University College London, London, United Kingdom
- * E-mail:
| | - Wahyu Wulaningsih
- MRC Unit for Lifelong Health and Ageing, Institute of Cardiovascular Science, University College London, London, United Kingdom
| | - Juan Castillo Fernandez
- Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
| | - George B. Ploubidis
- Centre for Longitudinal Studies, UCL Institute of Education, University College London, London, United Kingdom
| | - Alissa Goodman
- Centre for Longitudinal Studies, UCL Institute of Education, University College London, London, United Kingdom
| | - Jordana Bell
- Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
| | - Diana Kuh
- MRC Unit for Lifelong Health and Ageing, Institute of Cardiovascular Science, University College London, London, United Kingdom
| | - Rebecca Hardy
- MRC Unit for Lifelong Health and Ageing, Institute of Cardiovascular Science, University College London, London, United Kingdom
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28
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Miliku K, Azad MB. Breastfeeding and the Developmental Origins of Asthma: Current Evidence, Possible Mechanisms, and Future Research Priorities. Nutrients 2018; 10:E995. [PMID: 30061501 PMCID: PMC6115903 DOI: 10.3390/nu10080995] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2018] [Revised: 07/14/2018] [Accepted: 07/26/2018] [Indexed: 01/06/2023] Open
Abstract
Breastfeeding has many established health benefits, but its impact on asthma development is uncertain. Breastfeeding appears to have a positive and dose-dependent impact on respiratory health, particularly during early childhood and in high-risk populations; however, the strength and causality of these associations are unclear. It is challenging to compare results across studies due to methodological differences and biological variation. Resolving these inconsistencies will require well-designed, prospective studies that accurately capture asthma diagnoses and infant feeding exposures (including breastfeeding duration, exclusivity, and method of feeding), account for key confounders, evaluate dose effects, and consider effect modification and reverse causality. Mechanistic studies examining human milk bioactives and their impact on lung health and asthma development are beginning to emerge, and these will be important in establishing the causality and mechanistic basis of the observed associations between breastfeeding and asthma. In this review, we summarize current evidence on this topic, identify possible reasons for disagreement across studies, discuss potential mechanisms for a causal association, and provide recommendations for future research.
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Affiliation(s)
- Kozeta Miliku
- Manitoba Developmental Origins of Chronic Diseases in Children Network (DEVOTION), Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB R3E 3P4, Canada.
- Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB R3E 3P4, Canada.
| | - Meghan B Azad
- Manitoba Developmental Origins of Chronic Diseases in Children Network (DEVOTION), Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB R3E 3P4, Canada.
- Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB R3E 3P4, Canada.
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Alvarado-Cruz I, Alegría-Torres JA, Montes-Castro N, Jiménez-Garza O, Quintanilla-Vega B. Environmental Epigenetic Changes, as Risk Factors for the Development of Diseases in Children: A Systematic Review. Ann Glob Health 2018; 84:212-224. [PMID: 30873799 PMCID: PMC6748183 DOI: 10.29024/aogh.909] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Children are susceptible to environmental contaminants and are at risk of developing diseases, more so if the exposure begins at an early age. Epidemiological studies have postulated the hypothesis of the fetal origin of disease, which is mediated by epigenetic changes. Epigenetic marks are inheritable; they modulate the gene expression and can affect human health due to the presence of environmental factors. OBJECTIVE This review focuses on DNA-methylation and its association with environmental-related diseases in children. METHODS A search for studies related to DNA-methylation in children by pre- or post-natal environmental exposures was conducted, and those studies with appropriate designs and statistical analyses and evaluations of the exposure were selected. FINDINGS Prenatal and early life environmental factors, from diet to exposure to pollutants, have been associated with epigenetic changes, specifically DNA-methylation. Thus, maternal nutrition and smoking and exposure to air particulate matter, polycyclic aromatic hydrocarbons, arsenic, heavy metals, persistent organic pollutants, and some endocrine disrupters during pregnancy have been associated with genomic and gene-specific newborns' DNA-methylation changes that have shown in some cases sex-specific patterns. In addition, these maternal factors may deregulate the placental DNA-methylation balance and could induce a fetal reprogramming and later-in-life diseases. CONCLUSIONS Exposure to environmental pollutants during prenatal and early life can trigger epigenetic imbalances and eventually the development of diseases in children. The integration of epigenetic data should be considered in future risk assessments.
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Affiliation(s)
| | | | | | - Octavio Jiménez-Garza
- Health Sciences Division, University of Guanajuato, Leon Campus, Leon, Guanajuato, MX
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Honkova K, Rossnerova A, Pavlikova J, Svecova V, Klema J, Topinka J, Milcova A, Libalova H, Choi H, Veleminsky M, Sram RJ, Rossner P. Gene expression profiling in healthy newborns from diverse localities of the Czech Republic. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS 2018; 59:401-415. [PMID: 29602183 DOI: 10.1002/em.22184] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/01/2017] [Revised: 02/19/2018] [Accepted: 02/23/2018] [Indexed: 06/08/2023]
Abstract
Prenatal exposure to air pollution is associated with intrauterine growth restriction and low birth weight. Gene expression changes in newborns in relation to air pollution have not been sufficiently studied. We analyzed whole genome expression in cord blood leukocytes of 202 newborns from diverse localities of the Czech Republic, differing among other factors in levels of air pollution: the district of Karvina (characterized by higher concentration of air pollutants) and Ceske Budejovice (lower air pollution levels). We aimed to identify differentially expressed genes (DEGs) and pathways in relation to locality and concentration of air pollutants. We applied the linear model to identify the specific DEGs and the correlation analysis, to investigate the relationship between the concentrations of air pollutants and gene expression data. An analysis of biochemical pathways and gene set enrichment was also performed. In general, we observed modest changes of gene expression, mostly attributed to the effect of the locality. The highest number of DEGs was found in samples from the district of Karvina. A pathway analysis revealed a deregulation of processes associated with cell growth, apoptosis or cellular homeostasis, immune response-related processes or oxidative stress response. The association between concentrations of air pollutants and gene expression changes was weak, particularly for samples collected in Karvina. In summary, as we did not find a direct effect of exposure to air pollutants, we assume that the general differences in the environment, rather than actual concentrations of individual pollutants, represent a key factor affecting gene expression changes at delivery. Environ. Mol. Mutagen. 59:401-415, 2018. © 2018 Wiley Periodicals, Inc.
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Affiliation(s)
- Katerina Honkova
- Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic
| | - Andrea Rossnerova
- Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic
| | - Jitka Pavlikova
- Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic
| | - Vlasta Svecova
- Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic
| | - Jiri Klema
- Czech Technical University, Prague, Czech Republic
| | - Jan Topinka
- Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic
| | - Alena Milcova
- Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic
| | - Helena Libalova
- Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic
| | - Hyunok Choi
- School of Public Health, University at Albany, Rensselaer, New York
| | - Milos Veleminsky
- Faculty of Health and Social Studies, University of South Bohemia, Ceske Budejovice, Czech Republic
| | - Radim J Sram
- Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic
| | - Pavel Rossner
- Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic
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31
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Farzan N, Vijverberg SJ, Kabesch M, Sterk PJ, Maitland-van der Zee AH. The use of pharmacogenomics, epigenomics, and transcriptomics to improve childhood asthma management: Where do we stand? Pediatr Pulmonol 2018; 53:836-845. [PMID: 29493882 DOI: 10.1002/ppul.23976] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2017] [Accepted: 02/01/2018] [Indexed: 01/11/2023]
Abstract
Asthma is a complex multifactorial disease and it is the most common chronic disease in children. There is a high variability in response to asthma treatment, even in patients with good adherence to maintenance treatment, and a correct inhalation technique. Distinct underlying disease mechanisms in childhood asthma might be the reason of this heterogeneity. A deeper knowledge of the underlying molecular mechanisms of asthma has led to the recent development of advanced and mechanism-based treatments such as biologicals. However, biologicals are recommended only for patients with specific asthma phenotypes who remain uncontrolled despite high dosages of conventional asthma treatment. One of the main unmet needs in their application is lack of clinically available biomarkers to individualize pediatric asthma management and guide treatment. Pharmacogenomics, epigenomics, and transcriptomics are three omics fields that are rapidly advancing and can provide tools to identify novel asthma mechanisms and biomarkers to guide treatment. Pharmacogenomics focuses on variants in the DNA, epigenomics studies heritable changes that do not involve changes in the DNA sequence but lead to alteration of gene expression, and transcriptomics investigates gene expression by studying the complete set of mRNA transcripts in a cell or a population of cells. Advances in high-throughput technologies and statistical tools together with well-phenotyped patient inclusion and collaborations between different centers will expand our knowledge of underlying molecular mechanisms involved in disease onset and progress. Furthermore, it could help to select and stratify appropriate therapeutic strategies for subgroups of patients and hopefully bring precision medicine to daily practice.
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Affiliation(s)
- Niloufar Farzan
- Department of Respiratory Medicine, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands
| | - Susanne J Vijverberg
- Department of Respiratory Medicine, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands
| | - Michael Kabesch
- Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO), Regensburg, Germany
| | - Peter J Sterk
- Department of Respiratory Medicine, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands
| | - Anke H Maitland-van der Zee
- Department of Respiratory Medicine, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands
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Plusquin M, Chadeau-Hyam M, Ghantous A, Alfano R, Bustamante M, Chatzi L, Cuenin C, Gulliver J, Herceg Z, Kogevinas M, Nawrot TS, Pizzi C, Porta D, Relton CL, Richiardi L, Robinson O, Sunyer J, Vermeulen R, Vriens A, Vrijheid M, Henderson J, Vineis P. DNA Methylome Marks of Exposure to Particulate Matter at Three Time Points in Early Life. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2018; 52:5427-5437. [PMID: 29597345 DOI: 10.1021/acs.est.7b06447] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/17/2023]
Abstract
Maternal exposure to airborne particulate matter (PM) has been associated with restricted fetal growth and reduced birthweight. Here, we performed methylome-wide analyses of cord and children's blood DNA in relation to residential exposure to PM smaller than 10 μm (PM10). This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75). We could not identify significant CpG sites, by meta-analyzing associations between maternal PM10 exposure during pregnancy and DNA methylation in cord blood, nor by studying DNA methylation and concordant annual exposure at 7 and 15-17 years. The CpG cg21785536 was inversely associated with PM10 exposure using a longitudinal model integrating the three studied age groups (-1.2% per 10 μg/m3; raw p-value = 3.82 × 10-8). Pathway analyses on the corresponding genes of the 100 strongest associated CpG sites of the longitudinal model revealed enriched pathways relating to the GABAergic synapse, p53 signaling and NOTCH1. We provided evidence that residential PM10 exposure in early life affects methylation of the CpG cg21785536 located on the EGF Domain Specific O-Linked N-Acetylglucosamine Transferase gene.
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Affiliation(s)
- Michelle Plusquin
- Centre for Environmental Sciences , Hasselt University , Hasselt , Belgium
- Department of Epidemiology and Biostatistics, The School of Public Health , Imperial College London , London , United Kingdom
- Medical Research Council-Health Protection Agency Centre for Environment and Health , Imperial College London , London , United Kingdom
| | - Marc Chadeau-Hyam
- Department of Epidemiology and Biostatistics, The School of Public Health , Imperial College London , London , United Kingdom
- Medical Research Council-Health Protection Agency Centre for Environment and Health , Imperial College London , London , United Kingdom
- Institute for Risk Assessment Sciences (IRAS), Division of Environmental Epidemiology , Utrecht University , Utrecht , The Netherlands
| | - Akram Ghantous
- International Agency for Research on Cancer (IARC) , 150 Cours Albert-Thomas , 69008 Lyon , France
| | - Rossella Alfano
- Centre for Environmental Sciences , Hasselt University , Hasselt , Belgium
- Department of Epidemiology and Biostatistics, The School of Public Health , Imperial College London , London , United Kingdom
- Medical Research Council-Health Protection Agency Centre for Environment and Health , Imperial College London , London , United Kingdom
| | - Mariona Bustamante
- Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology , Barcelona , Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP) , Madrid , Spain
- ISGlobal, Centre for Research in Environmental Epidemiology (CREAL) , Barcelona , Spain
- Universitat Pompeu Fabra (UPF) , Barcelona, Catalonia , Spain
| | - Leda Chatzi
- Department of Preventive Medicine , University of Southern California , Los Angeles , California 90007 , United States
- Department of Social Medicine , University of Crete , Heraklion, Crete , Greece
| | - Cyrille Cuenin
- International Agency for Research on Cancer (IARC) , 150 Cours Albert-Thomas , 69008 Lyon , France
| | - John Gulliver
- Medical Research Council-Health Protection Agency Centre for Environment and Health , Imperial College London , London , United Kingdom
| | - Zdenko Herceg
- International Agency for Research on Cancer (IARC) , 150 Cours Albert-Thomas , 69008 Lyon , France
| | - Manolis Kogevinas
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP) , Madrid , Spain
- ISGlobal, Centre for Research in Environmental Epidemiology (CREAL) , Barcelona , Spain
- Universitat Pompeu Fabra (UPF) , Barcelona, Catalonia , Spain
- IMIM (Hospital del Mar Medical Research Institute) , Barcelona , Spain
| | - Tim S Nawrot
- Centre for Environmental Sciences , Hasselt University , Hasselt , Belgium
- Environment & Health Unit Leuven University , Leuven , Belgium
| | - Costanza Pizzi
- Cancer Epidemiology Unit-CERMS, Department of Medical Sciences , University of Turin and CPO-Piemonte , Torino , Italy
| | - Daniela Porta
- Department of Epidemiology of the Lazio Regional Health Service , Rome , Italy
| | - Caroline L Relton
- MRC Integrative Epidemiology Unit, Department of Population Health Sciences, Bristol Medical School , University of Bristol , Bristol , U.K
| | - Lorenzo Richiardi
- Cancer Epidemiology Unit-CERMS, Department of Medical Sciences , University of Turin and CPO-Piemonte , Torino , Italy
| | - Oliver Robinson
- Department of Epidemiology and Biostatistics, The School of Public Health , Imperial College London , London , United Kingdom
- Medical Research Council-Health Protection Agency Centre for Environment and Health , Imperial College London , London , United Kingdom
| | - Jordi Sunyer
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP) , Madrid , Spain
- ISGlobal, Centre for Research in Environmental Epidemiology (CREAL) , Barcelona , Spain
- IMIM (Hospital del Mar Medical Research Institute) , Barcelona , Spain
| | - Roel Vermeulen
- Medical Research Council-Health Protection Agency Centre for Environment and Health , Imperial College London , London , United Kingdom
- Institute for Risk Assessment Sciences (IRAS), Division of Environmental Epidemiology , Utrecht University , Utrecht , The Netherlands
| | - Annette Vriens
- Centre for Environmental Sciences , Hasselt University , Hasselt , Belgium
| | - Martine Vrijheid
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP) , Madrid , Spain
- ISGlobal, Centre for Research in Environmental Epidemiology (CREAL) , Barcelona , Spain
- Universitat Pompeu Fabra (UPF) , Barcelona, Catalonia , Spain
| | - John Henderson
- Department of Population Health Sciences, Bristol Medical School , University of Bristol , Bristol , U.K
| | - Paolo Vineis
- Centre for Environmental Sciences , Hasselt University , Hasselt , Belgium
- Department of Epidemiology and Biostatistics, The School of Public Health , Imperial College London , London , United Kingdom
- IIGM, Italian Institute for Genomic Medicine , Turin , Italy
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Fernández D, Sram RJ, Dostal M, Pastorkova A, Gmuender H, Choi H. Modeling Unobserved Heterogeneity in Susceptibility to Ambient Benzo[a]pyrene Concentration among Children with Allergic Asthma Using an Unsupervised Learning Algorithm. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2018; 15:E106. [PMID: 29320438 PMCID: PMC5800205 DOI: 10.3390/ijerph15010106] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Revised: 01/02/2018] [Accepted: 01/04/2018] [Indexed: 12/23/2022]
Abstract
Current studies of gene × air pollution interaction typically seek to identify unknown heritability of common complex illnesses arising from variability in the host's susceptibility to environmental pollutants of interest. Accordingly, a single component generalized linear models are often used to model the risk posed by an environmental exposure variable of interest in relation to a priori determined DNA variants. However, reducing the phenotypic heterogeneity may further optimize such approach, primarily represented by the modeled DNA variants. Here, we reduce phenotypic heterogeneity of asthma severity, and also identify single nucleotide polymorphisms (SNP) associated with phenotype subgroups. Specifically, we first apply an unsupervised learning algorithm method and a non-parametric regression to find a biclustering structure of children according to their allergy and asthma severity. We then identify a set of SNPs most closely correlated with each sub-group. We subsequently fit a logistic regression model for each group against the healthy controls using benzo[a]pyrene (B[a]P) as a representative airborne carcinogen. Application of such approach in a case-control data set shows that SNP clustering may help to partly explain heterogeneity in children's asthma susceptibility in relation to ambient B[a]P concentration with greater efficiency.
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Affiliation(s)
- Daniel Fernández
- Research and Development Unit, Parc Sanitari Sant Joan de Déu, Fundació Sant Joan de Déu, CIBERSAM, Dr. Antoni Pujadas, 42, Sant Boi de Llobregat, 08830 Barcelona, Spain.
- School of Mathematics and Statistics, Victoria University of Wellington, Wellington 6140, New Zealand.
| | - Radim J Sram
- Department of Genetic Ecotoxicology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, v.v.i., Vídeňská 1083, 142 20 Prague 4, Czech Republic.
| | - Miroslav Dostal
- Department of Genetic Ecotoxicology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, v.v.i., Vídeňská 1083, 142 20 Prague 4, Czech Republic.
| | - Anna Pastorkova
- Department of Genetic Ecotoxicology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, v.v.i., Vídeňská 1083, 142 20 Prague 4, Czech Republic.
| | - Hans Gmuender
- Genedata AG, Margarethenstrasse 38, CH-4053 Basel, Switzerland.
| | - Hyunok Choi
- Departments of Environmental Health Sciences, Epidemiology, and Biostatistics State University of New York at Albany School of Public Health, Rensselaer, NY 12144, USA.
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Choi H, Tabashidze N, Rossner P, Dostal M, Pastorkova A, Kong SW, Gmuender H, Sram RJ. Altered vulnerability to asthma at various levels of ambient Benzo[a]Pyrene by CTLA4, STAT4 and CYP2E1 polymorphisms. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2017; 231:1134-1144. [PMID: 28807506 DOI: 10.1016/j.envpol.2017.07.057] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Revised: 07/17/2017] [Accepted: 07/18/2017] [Indexed: 06/07/2023]
Abstract
BACKGROUND Within fossil- and solid-fuel dependent geographic locations, mechanisms of air pollution-induced asthma remains unknown. In particular, sources of greater genetic susceptibility to airborne carcinogen, namely, benzo[a]pyrene (B[a]P) has never been investigated beyond that of a few well known genes. OBJECTIVES To deepen our understanding on how the genotypic variations within the candidate genes contribute to the variability in the children's susceptibility to ambient B[a]P on doctor-diagnosed asthma. METHODS Clinically confirmed asthmatic versus healthy control children (aged, 7-15) were enrolled from historically polluted and rural background regions in Czech Republic. Contemporaneous ambient B[a]P concentration was obtained from the routine monitoring network. The sputum DNA was genotyped for 95 genes. B[a]P interaction with SNPs was studied by two-stage, semi-agnostic screening of 621 SNPs. RESULTS The median B[a]P within the highly polluted urban center was 8-times higher than that in the background region (7.8 vs. 1.1 ng/m3) during the period of investigation. Within the baseline model, which considered B[a]P exposure-only, the second tertile range was associated with a significantly reduced odds (aOR = 0.28) of asthma (95% CI, 0.16 to 0.50) compared to those at the lowest range. However, the highest range of B[a]P was associated with 3.18-times greater odds of the outcome (95% CI, 1.77 to 5.71). Within the gene-environment interaction models, joint occurrence of a high B[a]P exposure range and having a high-risk genotype at CTLA4 gene (rs11571316) was associated with 9-times greater odds (95% CI, 4.56-18.36) of the asthma diagnosis. Similarly, rs11571319 at CTLA4 and a high B[a]P exposure range was associated with a 8-times greater odds (95% CI, 3.95-14.27) of asthma diagnosis. Furthermore, having TG + GG genotypes on rs1031509 near STAT4 was associated with 5-times (95% CI, 3.03-8.55) greater odds of asthma diagnosis at the highest B[a]P range, compared to the odds at the reference range. Also CYP2E1 AT + TT genotypes (rs2070673) was associated with 5-times (95% CI, 3.1-8.8) greater odds of asthma diagnosis at the highest B[a]P exposure. CONCLUSIONS The children, who jointly experience a high B[a]P exposure (6.3-8.5 ng/m3) as well as susceptible genotypes in CTLA4 (rs11571316 and rs11571319), STAT4 (rs1031509), and CYP2E1 (rs2070673), respectively, are associated with a significantly greater odds of having doctor-diagnosed asthma, compared to those with neither risk factors.
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Affiliation(s)
- Hyunok Choi
- Departments of Environmental Health Sciences, Epidemiology, and Biostatistics University at Albany School of Public Health, One University Place, Room 153, Rensselaer, NY 12144-3456, USA.
| | - Nana Tabashidze
- Department of Genetic Ecotoxicology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, v.v.i., Vídeňská 1083, 142 20, Prague 4, Czech Republic.
| | - Pavel Rossner
- Department of Genetic Ecotoxicology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, v.v.i., Vídeňská 1083, 142 20, Prague 4, Czech Republic.
| | - Miroslav Dostal
- Department of Genetic Ecotoxicology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, v.v.i., Vídeňská 1083, 142 20, Prague 4, Czech Republic.
| | - Anna Pastorkova
- Department of Genetic Ecotoxicology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, v.v.i., Vídeňská 1083, 142 20, Prague 4, Czech Republic
| | - Sek Won Kong
- Boston Children's Hospital, 300 Longwood Ave, Boston, MA 02115, USA.
| | - Hans Gmuender
- Genedata AG, Margarethenstrasse 38, CH-4053, Basel, Switzerland.
| | - Radim J Sram
- Department of Genetic Ecotoxicology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, v.v.i., Vídeňská 1083, 142 20, Prague 4, Czech Republic.
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Rossnerova A, Pokorna M, Svecova V, Sram RJ, Topinka J, Zölzer F, Rossner P. Adaptation of the human population to the environment: Current knowledge, clues from Czech cytogenetic and "omics" biomonitoring studies and possible mechanisms. MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH 2017; 773:188-203. [PMID: 28927528 DOI: 10.1016/j.mrrev.2017.07.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Revised: 07/10/2017] [Accepted: 07/11/2017] [Indexed: 12/19/2022]
Abstract
The human population is continually exposed to numerous harmful environmental stressors, causing negative health effects and/or deregulation of biomarker levels. However, studies reporting no or even positive impacts of some stressors on humans are also sometimes published. The main aim of this review is to provide a comprehensive overview of the last decade of Czech biomonitoring research, concerning the effect of various levels of air pollution (benzo[a]pyrene) and radiation (uranium, X-ray examination and natural radon background), on the differently exposed population groups. Because some results obtained from cytogenetic studies were opposite than hypothesized, we have searched for a meaningful interpretation in genomic/epigenetic studies. A detailed analysis of our data supported by the studies of others and current epigenetic knowledge, leads to a hypothesis of the versatile mechanism of adaptation to environmental stressors via DNA methylation settings which may even originate in prenatal development, and help to reduce the resulting DNA damage levels. This hypothesis is fully in agreement with unexpected data from our studies (e.g. lower levels of DNA damage in subjects from highly polluted regions than in controls or in subjects exposed repeatedly to a pollutant than in those without previous exposure), and is also supported by differences in DNA methylation patterns in groups from regions with various levels of pollution. In light of the adaptation hypothesis, the following points may be suggested for future research: (i) the chronic and acute exposure of study subjects should be distinguished; (ii) the exposure history should be mapped including place of residence during the life and prenatal development; (iii) changes of epigenetic markers should be monitored over time. In summary, investigation of human adaptation to the environment, one of the most important processes of survival, is a new challenge for future research in the field of human biomonitoring that may change our view on the results of biomarker analyses and potential negative health impacts of the environment.
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Affiliation(s)
- Andrea Rossnerova
- Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine, Czech Academy of Sciences, 14220 Prague 4, Czech Republic
| | - Michaela Pokorna
- Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine, Czech Academy of Sciences, 14220 Prague 4, Czech Republic
| | - Vlasta Svecova
- Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine, Czech Academy of Sciences, 14220 Prague 4, Czech Republic
| | - Radim J Sram
- Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine, Czech Academy of Sciences, 14220 Prague 4, Czech Republic
| | - Jan Topinka
- Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine, Czech Academy of Sciences, 14220 Prague 4, Czech Republic
| | - Friedo Zölzer
- Institute of Radiology, Toxicology and Civil Protection, University of South Bohemia, 37005 Ceske Budejovice, Czech Republic
| | - Pavel Rossner
- Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine, Czech Academy of Sciences, 14220 Prague 4, Czech Republic.
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van Meel ER, de Jong M, Elbert NJ, den Dekker HT, Reiss IK, de Jongste JC, Jaddoe VWV, Duijts L. Duration and exclusiveness of breastfeeding and school-age lung function and asthma. Ann Allergy Asthma Immunol 2017; 119:21-26.e2. [PMID: 28554704 DOI: 10.1016/j.anai.2017.05.002] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Revised: 04/25/2017] [Accepted: 05/01/2017] [Indexed: 11/18/2022]
Abstract
BACKGROUND Breastfeeding reduces the risk of asthma in early childhood, but it is not clear whether its effect on respiratory morbidity is still present in later childhood. OBJECTIVE To examine the associations of any breastfeeding, breastfeeding duration, and breastfeeding exclusiveness with lung function and asthma in school-aged children and whether associations were influenced by respiratory tract infections and maternal or child's atopic status. METHODS This study of 4,464 children was embedded in a population-based prospective cohort study. Information on breastfeeding was obtained by multiple questionnaires from birth until 1 year of age. At 10 years of age, lung function was measured by spirometry, and information on asthma was obtained by questionnaire. Adjusted linear and logistic regression models were used to examine the associations. RESULTS Shorter duration of breastfeeding was associated with a lower forced expiratory volume in 1 second (FEV1) only (z score change, -0.01; 95% confidence interval [CI], -0.02 to -0.00) per month shorter breastfeeding, but not asthma. When categorized, breastfeeding for 2 to 4 months was associated with a lower forced vital capacity (FVC) (z score change, -0.11; 95% CI, -0.20 to -0.03) compared with breastfeeding for 6 months or longer. Nonexclusive breastfeeding for 4 months was associated with a lower FVC (z score change, -0.08; 95% CI, -0.16 to -0.01) compared with exclusive breastfeeding for 4 months. Results did not materially change after additional adjustment for lower respiratory tract infections and were not modified by maternal history of asthma or atopy, child's eczema, or inhalant allergic sensitization. CONCLUSION Shorter duration and nonexclusivity of breastfeeding were associated with a lower FEV1 and FVC but not asthma at school-age.
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Affiliation(s)
- Evelien R van Meel
- The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Division of Respiratory Medicine and Allergology, Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Mandy de Jong
- The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Division of Respiratory Medicine and Allergology, Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Niels J Elbert
- The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Dermatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Herman T den Dekker
- The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Division of Respiratory Medicine and Allergology, Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Irwin K Reiss
- Division of Neonatology, Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Johan C de Jongste
- Division of Respiratory Medicine and Allergology, Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Vincent W V Jaddoe
- The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Liesbeth Duijts
- Division of Respiratory Medicine and Allergology, Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Division of Neonatology, Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
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37
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Jung KH, Torrone D, Lovinsky-Desir S, Perzanowski M, Bautista J, Jezioro JR, Hoepner L, Ross J, Perera FP, Chillrud SN, Miller RL. Short-term exposure to PM 2.5 and vanadium and changes in asthma gene DNA methylation and lung function decrements among urban children. Respir Res 2017; 18:63. [PMID: 28424066 PMCID: PMC5397738 DOI: 10.1186/s12931-017-0550-9] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2017] [Accepted: 04/11/2017] [Indexed: 12/24/2022] Open
Abstract
Background Both short and long-term exposure to traffic-related air pollutants have been associated with asthma and reduced lung function. We hypothesized that short-term indoor exposure to fine particulate matter <2.5 μm (PM2.5) and vanadium (V) would be associated with altered buccal cell DNA methylation of targeted asthma genes and decreased lung function among urban children in a nested subcohort of African American and Dominican children. Methods Six day integrated levels of air pollutants were measured from children’s homes (age 9–14; n = 163), repeated 6 months later (n = 98). Buccal samples were collected repeatedly during visits. CpG promoter loci of asthma genes (i.e., interleukin 4 (IL4), interferon gamma (IFNγ), inducible nitric oxide synthase (NOS2A), arginase 2 (ARG2)) were pyrosequenced and lung function was assessed. Results Exposure to V, but not PM2.5, was associated with lower DNA methylation of IL4 and IFNγ. In exploratory analyses, V levels were associated with lower methylation of the proinflammatory NOS2A-CpG+5099 among asthmatic overweight or obese children but not nonasthmatics. Short-term exposure to PM2.5, but not V, appeared associated with lower lung function (i.e., reduced z-scores for forced expiratory volume in one second (FEV1, FEV1/ forced vital capacity [FEV1/FVC] and forced expiratory flow at 25–75% of FVC [FEF25–75]). Conclusions Exposure to V was associated with altered DNA methylation of allergic and proinflammatory asthma genes implicated in air pollution related asthma. However, short-term exposure to PM2.5, but not V, appeared associated with decrements in lung function among urban children. Electronic supplementary material The online version of this article (doi:10.1186/s12931-017-0550-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Kyung Hwa Jung
- Division of Pulmonary, Allergy and Critical Care of Medicine, Department of Medicine, College of Physicians and Surgeons, Columbia University, PH8E-101, 630 W. 168 St., New York, NY, 10032, USA.
| | - David Torrone
- Division of Pulmonary, Allergy and Critical Care of Medicine, Department of Medicine, College of Physicians and Surgeons, Columbia University, PH8E-101, 630 W. 168 St., New York, NY, 10032, USA
| | - Stephanie Lovinsky-Desir
- Division of Pediatric Pulmonary, Department of Pediatrics, College of Physicians and Surgeons, Columbia University, 630 W. 168 St., New York, NY, 10032, USA
| | - Matthew Perzanowski
- Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 722 W. 168 St., New York, NY, 10032, USA
| | - Joshua Bautista
- Division of Pulmonary, Allergy and Critical Care of Medicine, Department of Medicine, College of Physicians and Surgeons, Columbia University, PH8E-101, 630 W. 168 St., New York, NY, 10032, USA
| | - Jacqueline R Jezioro
- Division of Pulmonary, Allergy and Critical Care of Medicine, Department of Medicine, College of Physicians and Surgeons, Columbia University, PH8E-101, 630 W. 168 St., New York, NY, 10032, USA
| | - Lori Hoepner
- Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 722 W. 168 St., New York, NY, 10032, USA
| | - Jamie Ross
- Lamont-Doherty Earth Observatory, Columbia University, 61 Rt, 9 W Palisades, New York, 10964, USA
| | - Frederica P Perera
- Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 722 W. 168 St., New York, NY, 10032, USA
| | - Steven N Chillrud
- Lamont-Doherty Earth Observatory, Columbia University, 61 Rt, 9 W Palisades, New York, 10964, USA
| | - Rachel L Miller
- Division of Pulmonary, Allergy and Critical Care of Medicine, Department of Medicine, College of Physicians and Surgeons, Columbia University, PH8E-101, 630 W. 168 St., New York, NY, 10032, USA.,Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 722 W. 168 St., New York, NY, 10032, USA.,Division of Pediatric Allergy, Immunology and Rheumatology, Department of Pediatrics, College of Physicians and Surgeons, Columbia University, PH8E-101, 630 W. 168 St., New York, NY, 10032, USA
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38
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DeVries A, Vercelli D. The neonatal methylome as a gatekeeper in the trajectory to childhood asthma. Epigenomics 2017; 9:585-593. [PMID: 28322586 DOI: 10.2217/epi-2016-0149] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Asthma is a heterogeneous group of conditions that typically begin in early life and result in recurrent, reversible bronchial obstruction. The role played by epigenetic mechanisms in the pathogenesis of childhood asthma is understood only in part. Here we discuss asthma epigenetics within a developmental perspective based on our recent demonstration that the epigenetic trajectory to childhood asthma begins at birth. We next discuss how this trajectory may be affected by prenatal environmental exposures. Finally, we examine in vitro studies that model the impact of asthma-associated exposures on the epigenome. All of these studies specifically surveyed human DNA methylation and involved a genome-wide component. In combination, their results broaden our understanding of asthma pathogenesis and the role the methylome plays in this process.
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Affiliation(s)
- Avery DeVries
- Graduate Program in Cellular & Molecular Medicine, University of Arizona, Tucson, AZ, USA.,Asthma & Airway Disease Research Center, University of Arizona, Tucson, AZ, USA
| | - Donata Vercelli
- Asthma & Airway Disease Research Center, University of Arizona, Tucson, AZ, USA.,Arizona Center for the Biology of Complex Diseases, University of Arizona, Tucson, AZ, USA.,Department of Cellular & Molecular Medicine, University of Arizona, Tucson, AZ, USA.,The Bio5 Institute, University of Arizona, Tucson, AZ, USA
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39
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Potaczek DP, Harb H, Michel S, Alhamwe BA, Renz H, Tost J. Epigenetics and allergy: from basic mechanisms to clinical applications. Epigenomics 2017; 9:539-571. [PMID: 28322581 DOI: 10.2217/epi-2016-0162] [Citation(s) in RCA: 191] [Impact Index Per Article: 23.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Allergic diseases are on the rise in the Western world and well-known allergy-protecting and -driving factors such as microbial and dietary exposure, pollution and smoking mediate their influence through alterations of the epigenetic landscape. Here, we review key facts on the involvement of epigenetic modifications in allergic diseases and summarize and critically evaluate the lessons learned from epigenome-wide association studies. We show the potential of epigenetic changes for various clinical applications: as diagnostic tools, to assess tolerance following immunotherapy or possibly predict the success of therapy at an early time point. Furthermore, new technological advances such as epigenome editing and DNAzymes will allow targeted alterations of the epigenome in the future and provide novel therapeutic tools.
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Affiliation(s)
- Daniel P Potaczek
- Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Philipps-Universität Marburg, Marburg, Germany.,International Inflammation (in-FLAME) Network, Worldwide Universities Network (WUN).,German Centre for Lung Research (DZL).,John Paul II Hospital, Krakow, Poland
| | - Hani Harb
- Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Philipps-Universität Marburg, Marburg, Germany.,International Inflammation (in-FLAME) Network, Worldwide Universities Network (WUN).,German Centre for Lung Research (DZL)
| | - Sven Michel
- Secarna Pharmaceuticals GmbH & Co KG, Planegg, Germany
| | - Bilal Alashkar Alhamwe
- Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Philipps-Universität Marburg, Marburg, Germany
| | - Harald Renz
- Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Philipps-Universität Marburg, Marburg, Germany.,International Inflammation (in-FLAME) Network, Worldwide Universities Network (WUN).,German Centre for Lung Research (DZL)
| | - Jörg Tost
- Laboratory for Epigenetics & Environment, Centre National de Génotypage, CEA-Institut de Génomique, Evry, France
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40
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Hartwig FP, Loret de Mola C, Davies NM, Victora CG, Relton CL. Breastfeeding effects on DNA methylation in the offspring: A systematic literature review. PLoS One 2017; 12:e0173070. [PMID: 28257446 PMCID: PMC5336253 DOI: 10.1371/journal.pone.0173070] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2016] [Accepted: 02/14/2017] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Breastfeeding benefits both infants and mothers. Recent research shows long-term health and human capital benefits among individuals who were breastfed. Epigenetic mechanisms have been suggested as potential mediators of the effects of early-life exposures on later health outcomes. We reviewed the literature on the potential effects of breastfeeding on DNA methylation. METHODS Studies reporting original results and evaluating DNA methylation differences according to breastfeeding/breast milk groups (e.g., ever vs. never comparisons, different categories of breastfeeding duration, etc) were eligible. Six databases were searched simultaneously using Ovid, and the resulting studies were evaluated independently by two reviewers. RESULTS Seven eligible studies were identified. Five were conducted in humans. Studies were heterogeneous regarding sample selection, age, target methylation regions, methylation measurement and breastfeeding categorisation. Collectively, the studies suggest that breastfeeding might be negatively associated with promoter methylation of LEP (which encodes an anorexigenic hormone), CDKN2A (involved in tumour suppression) and Slc2a4 genes (which encodes an insulin-related glucose transporter) and positively with promoter methylation of the Nyp (which encodes an orexigenic neuropeptide) gene, as well as influence global methylation patterns and modulate epigenetic effects of some genetic variants. CONCLUSIONS The findings from our systematic review are far from conclusive due to the small number of studies and their inherent limitations. Further studies are required to understand the actual potential role of epigenetics in the associations of breastfeeding with later health outcomes. Suggestions for future investigations, focusing on epigenome-wide association studies, are provided.
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Affiliation(s)
- Fernando Pires Hartwig
- Postgraduate Programme in Epidemiology, Federal University of Pelotas, Pelotas, Brazil
- MRC Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom
- * E-mail:
| | | | - Neil Martin Davies
- MRC Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom
- School of Social and Community Medicine, University of Bristol, United Kingdom
| | - Cesar Gomes Victora
- Postgraduate Programme in Epidemiology, Federal University of Pelotas, Pelotas, Brazil
| | - Caroline L. Relton
- MRC Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom
- School of Social and Community Medicine, University of Bristol, United Kingdom
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41
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Dose- and time- effect responses of DNA methylation and histone H3K9 acetylation changes induced by traffic-related air pollution. Sci Rep 2017; 7:43737. [PMID: 28256616 PMCID: PMC5335614 DOI: 10.1038/srep43737] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2016] [Accepted: 01/30/2017] [Indexed: 11/08/2022] Open
Abstract
As an important risk factor of respiratory disorders, traffic-related air pollution (TRAP) has caused extensive concerns. Epigenetic change has been considered a link between TRAP and respiratory diseases. However, the exact effects of TRAP on epigenetic changes are still unclear. Here we investigated the dose- and time- effect responses of TRAP on DNA methylations and H3K9 acetylation (H3K9ac) in both blood and lung tissues of rats. The findings showed that every 1 μg/m3 increase of TRAP components were associated with changes in %5 mC (95% CI) in LINE-1, iNOS, p16CDKN2A, and APC ranging from −0.088% (−0.150, −0.026) to 0.102 (0.049, 0.154), as well as 0.276 (0.053, 0.498) to 0.475 (0.103, 0.848) ng/mg increase of H3K9ac. In addition, every 1 more day exposure at high level of TRAP (in tunnel) also significantly changed the levels of DNA methylation (ranging from −0.842% to 0.248%) and H3K9ac (16.033 and 15.718 ng/mg pro in PBMC and lung tissue, respectively) changes. Season and/or sex could interact with air pollutants in affecting DNA methylation and H3K9ac. The findings showed that TRAP exposure is dose- and time- dependently associated with the changes of DNA methylation and H3K9ac.
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42
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Maghbooli Z, Hossein-Nezhad A, Ramezani M, Moattari S. Epigenetic Alterations and Exposure to Air Pollutants: Protocol for a Birth Cohort Study to Evaluate the Association Between Adverse Birth Outcomes and Global DNA Methylation. JMIR Res Protoc 2017; 6:e29. [PMID: 28232302 PMCID: PMC5344983 DOI: 10.2196/resprot.7114] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2016] [Revised: 01/22/2017] [Accepted: 01/23/2017] [Indexed: 12/17/2022] Open
Abstract
Background Prenatal exposure to air pollutants can increase the risk of adverse birth outcomes and susceptibility to a number of complex disorders later in life. Despite this general understanding, the molecular and cellular responses to air pollution exposure during early life are not completely clear. Objective The aims of this study are to test the association between air pollution and adverse pregnancy outcomes, and to determine whether the levels of maternal and cord blood and of placental DNA methylation during pregnancy predict adverse birth outcomes in polluted areas. Methods This is a birth cohort study. We will enroll pregnant healthy women attending prenatal care clinics in Tehran, Iran, who are resident in selected polluted and unpolluted regions before the 14th week of pregnancy. We will calculate the regional background levels of fine particulate matter (particles with a diameter between 2.5 and 10 μm) and nitrogen dioxide for all regions of by using data from the Tehran Air Quality Control Company. Then, we will select 2 regions as the polluted and unpolluted areas of interest. Healthy mothers living in the selected polluted and non polluted regions will be enrolled in this study. A maternal health history questionnaire will be completed at each trimester. During the first and second trimester, we will draw mothers’ blood for biochemical and DNA methylation analyses. At the time of delivery time, we will collect maternal and cord blood for biochemical, gene expression, and DNA methylation analyses. We will also record birth outcomes (the newborn’s sex, birth date, birth weight and length, gestational age, Apgar score, and level of neonatal care required). Results The project was funded in March 2016 and enrollment will be completed in August 2017. Data analysis is under way, and the first results are expected to be submitted for publication in November 2017. Conclusions We supposed that prenatal exposures to air pollutants can influence fetal reprogramming by epigenetic modifications such as DNA methylation. This could explain the association between air pollution and adverse pregnancy outcomes.
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Affiliation(s)
- Zhila Maghbooli
- Osteoporosis Research Center, Endocrinology and Metabolism Research Institute of Tehran University of Medical Sciences, Tehran, Islamic Republic Of Iran
| | - Arash Hossein-Nezhad
- Osteoporosis Research Center, Endocrinology and Metabolism Research Institute of Tehran University of Medical Sciences, Tehran, Islamic Republic Of Iran.,Department of Medicine, Section of Endocrinology, Nutrition, and Diabetes, Vitamin D, Skin and Bone Research Laboratory, Boston University Medical Center, Boston, MA, United States
| | - Majid Ramezani
- Department of Endocrinology, Baghiatallah University of Medical Sciences, Tehran, Islamic Republic Of Iran
| | - Syamak Moattari
- Osteoporosis Research Center, Endocrinology and Metabolism Research Institute of Tehran University of Medical Sciences, Tehran, Islamic Republic Of Iran.,Health Science Department, Worcester State University, Worcester, MA, United States
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43
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Gruzieva O, Xu CJ, Breton CV, Annesi-Maesano I, Antó JM, Auffray C, Ballereau S, Bellander T, Bousquet J, Bustamante M, Charles MA, de Kluizenaar Y, den Dekker HT, Duijts L, Felix JF, Gehring U, Guxens M, Jaddoe VV, Jankipersadsing SA, Merid SK, Kere J, Kumar A, Lemonnier N, Lepeule J, Nystad W, Page CM, Panasevich S, Postma D, Slama R, Sunyer J, Söderhäll C, Yao J, London SJ, Pershagen G, Koppelman GH, Melén E. Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO2 Air Pollution Exposure. ENVIRONMENTAL HEALTH PERSPECTIVES 2017; 125:104-110. [PMID: 27448387 PMCID: PMC5226705 DOI: 10.1289/ehp36] [Citation(s) in RCA: 166] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/26/2016] [Revised: 06/13/2016] [Accepted: 06/22/2016] [Indexed: 05/04/2023]
Abstract
BACKGROUND Prenatal exposure to air pollution is considered to be associated with adverse effects on child health. This may partly be mediated by mechanisms related to DNA methylation. OBJECTIVES We investigated associations between exposure to air pollution, using nitrogen dioxide (NO2) as marker, and epigenome-wide cord blood DNA methylation. METHODS We meta-analyzed the associations between NO2 exposure at residential addresses during pregnancy and cord blood DNA methylation (Illumina 450K) in four European and North American studies (n = 1,508) with subsequent look-up analyses in children ages 4 (n = 733) and 8 (n = 786) years. Additionally, we applied a literature-based candidate approach for antioxidant and anti-inflammatory genes. To assess influence of exposure at the transcriptomics level, we related mRNA expression in blood cells to NO2 exposure in 4- (n = 111) and 16-year-olds (n = 239). RESULTS We found epigenome-wide significant associations [false discovery rate (FDR) p < 0.05] between maternal NO2 exposure during pregnancy and DNA methylation in newborns for 3 CpG sites in mitochondria-related genes: cg12283362 (LONP1), cg24172570 (3.8 kbp upstream of HIBADH), and cg08973675 (SLC25A28). The associations with cg08973675 methylation were also significant in the older children. Further analysis of antioxidant and anti-inflammatory genes revealed differentially methylated CpGs in CAT and TPO in newborns (FDR p < 0.05). NO2 exposure at the time of biosampling in childhood had a significant impact on CAT and TPO expression. CONCLUSIONS NO2 exposure during pregnancy was associated with differential offspring DNA methylation in mitochondria-related genes. Exposure to NO2 was also linked to differential methylation as well as expression of genes involved in antioxidant defense pathways. Citation: Gruzieva O, Xu CJ, Breton CV, Annesi-Maesano I, Antó JM, Auffray C, Ballereau S, Bellander T, Bousquet J, Bustamante M, Charles MA, de Kluizenaar Y, den Dekker HT, Duijts L, Felix JF, Gehring U, Guxens M, Jaddoe VV, Jankipersadsing SA, Merid SK, Kere J, Kumar A, Lemonnier N, Lepeule J, Nystad W, Page CM, Panasevich S, Postma D, Slama R, Sunyer J, Söderhäll C, Yao J, London SJ, Pershagen G, Koppelman GH, Melén E. 2017. Epigenome-wide meta-analysis of methylation in children related to prenatal NO2 air pollution exposure. Environ Health Perspect 125:104-110; http://dx.doi.org/10.1289/EHP36.
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Affiliation(s)
- Olena Gruzieva
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
- Address corresponence to O. Gruzieva, Institute of Environmental Medicine, Karolinska Institutet, Nobels väg 13, SE-17177 Stockholm, Sweden. Telephone: 46852480022. E-mail:
| | - Cheng-Jian Xu
- Groningen Research Institute for Asthma and COPD (GRIAC), Department of Pulmonology, and
- Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Carrie V. Breton
- Department of Preventive Medicine, University of Southern California, Los Angeles, California, USA
| | - Isabella Annesi-Maesano
- Department of Epidemiology of Allergic and Respiratory Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France
| | - Josep M. Antó
- ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain
- IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain
- Universitat Pompeu Fabra (UPF), Barcelona, Spain
- CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
| | - Charles Auffray
- European Institute for Systems Biology and Medicine, Université de Lyon, Lyon, France
| | - Stéphane Ballereau
- European Institute for Systems Biology and Medicine, Université de Lyon, Lyon, France
| | - Tom Bellander
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
- Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden
| | - Jean Bousquet
- CHU (Centre Hospitalier Universitaire) Montpellier, University of Montpellier, Montpellier, France
| | - Mariona Bustamante
- ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain
- Universitat Pompeu Fabra (UPF), Barcelona, Spain
- CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
- Center for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, Spain
| | - Marie-Aline Charles
- Early Origin of the Child’s Health And Development (ORCHAD) team, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS-UMR1153) Inserm, Université Paris Descartes, Villejuif, France
| | - Yvonne de Kluizenaar
- The Netherlands Organization for Applied Scientific Research (TNO), Delft, the Netherlands
| | - Herman T. den Dekker
- Generation R Study Group,
- Department of Epidemiology, and
- Department of Pediatrics, Erasmus MC (Medical Centre), University Medical Center, Rotterdam, the Netherlands
| | - Liesbeth Duijts
- Generation R Study Group,
- Department of Epidemiology, and
- Department of Pediatrics, Erasmus MC (Medical Centre), University Medical Center, Rotterdam, the Netherlands
| | - Janine F. Felix
- Generation R Study Group,
- Department of Epidemiology, and
- Department of Pediatrics, Erasmus MC (Medical Centre), University Medical Center, Rotterdam, the Netherlands
| | - Ulrike Gehring
- Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands
| | - Mònica Guxens
- ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain
- Universitat Pompeu Fabra (UPF), Barcelona, Spain
- CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
- Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Centre–Sophia Children’s Hospital, Rotterdam, the Netherlands
| | - Vincent V.W. Jaddoe
- Generation R Study Group,
- Department of Epidemiology, and
- Department of Pediatrics, Erasmus MC (Medical Centre), University Medical Center, Rotterdam, the Netherlands
| | - Soesma A. Jankipersadsing
- Groningen Research Institute for Asthma and COPD (GRIAC), Department of Pulmonology, and
- Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Simon Kebede Merid
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Juha Kere
- Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
| | - Ashish Kumar
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
- Unit of Chronic Disease Epidemiology, Department of Public Health Epidemiology, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Nathanael Lemonnier
- European Institute for Systems Biology and Medicine, Université de Lyon, Lyon, France
| | - Johanna Lepeule
- Team of Environmental Epidemiology, Inserm and University Grenoble-Alpes, IAB (U1209), Grenoble, France
| | - Wenche Nystad
- Division for Physical and Mental health, Norwegian Institute of Public Health, Oslo, Norway
| | - Christian Magnus Page
- Division for Physical and Mental health, Norwegian Institute of Public Health, Oslo, Norway
| | - Sviatlana Panasevich
- Division for Physical and Mental health, Norwegian Institute of Public Health, Oslo, Norway
| | - Dirkje Postma
- Groningen Research Institute for Asthma and COPD (GRIAC), Department of Pulmonology, and
| | - Rémy Slama
- Team of Environmental Epidemiology, Inserm and University Grenoble-Alpes, IAB (U1209), Grenoble, France
| | - Jordi Sunyer
- ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain
- IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain
- Universitat Pompeu Fabra (UPF), Barcelona, Spain
- CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
| | - Cilla Söderhäll
- Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
- Department of Women´s and Children´s Health, Karolinska Institutet, Stockholm, Sweden
| | - Jin Yao
- Department of Preventive Medicine, University of Southern California, Los Angeles, California, USA
| | - Stephanie J. London
- Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA
| | - Göran Pershagen
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
- Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden
| | - Gerard H. Koppelman
- Groningen Research Institute for Asthma and COPD (GRIAC), Beatrix Children’s Hospital, Department of Pediatric Pulmonology and Pediatric Allergology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Erik Melén
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
- Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden
- Sachs Children’s Hospital, Stockholm, Sweden
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Abstract
PURPOSE OF REVIEW The goal of this review was to systematically analyze recent studies updating our knowledge on the role of epigenetic mechanisms in childhood asthma. RECENT FINDINGS A systematic literature search was conducted that identified 23 fresh articles published within the last 5 years reporting the results of human studies on the relationships between epigenetic modifications and childhood asthma or its/related phenotypes. In almost all these studies, meaningful associations between levels of epigenetic marks (DNA methylation and/or histone modifications) and pediatric asthma or its/related phenotypes have been observed. In addition, many studies identified by our screening analyzed those associations in the context of environmental factors, such as pollution, tobacco smoke, farming, or diet, showing in a huge majority a modifying effect of those exposures. SUMMARY The results of our systematic literature search provide a strong support for the role of epigenetic mechanisms in (mediating the effects of environmental exposure on) pediatric asthma. This knowledge may possibly be translated into diagnostic and/or therapeutic approaches.
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Rossnerova A, Honkova K, Pavlikova J, Skalicka ZF, Havrankova R, Solansky I, Rossner P, Sram RJ, Zölzer F. Mapping the factors affecting the frequency and types of micronuclei in an elderly population from Southern Bohemia. Mutat Res 2016; 793-794:32-40. [PMID: 27810620 DOI: 10.1016/j.mrfmmm.2016.10.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2016] [Revised: 09/11/2016] [Accepted: 10/22/2016] [Indexed: 06/06/2023]
Abstract
The micronucleus assay is one of the most common methods used to assess chromosomal damage (losses or breaks) in human peripheral blood lymphocytes (PBL) in genetic toxicology. Most studies have focused on analyzing total micronuclei (MN), but identifying the content of MN can provide more detailed information. The main aim of this study was to map the factors affecting the frequency and types of micronuclei in binucleated cells (BNC) in elderly population. Fluorescence in situ hybridization using Human Pan Centromeric Chromosome Paint was used to identify centromere positive (CEN+) or centromere negative (CEN-) MN. A group of 95 men from Southern Bohemia, Czech Republic (average age 68.0±6.8 years) was followed repeatedly, in spring and fall 2014. The study participants were former workers of the uranium plant "MAPE Mydlovary" (processing uranium ore from 1962 to 1991), and controls. The general profile of individual types of MN, and the effect of the season, former uranium exposure, age, smoking status, weight, and X-ray examination on the level and type of MN were analyzed. The results of this study showed: (i) a stable profile of BNC with MN based on the number of MN during two seasons; (ii) an increase of the number of CEN+ MN from spring to fall; (iii) a lower frequency of the total MN in the exposed group than in controls with a significant difference in the percentage of aberrant cells (%AB.C.) in the fall; (iv) no clear effect of age, smoking and BMI on DNA damage in this group; (v) lower DNA damage levels in former uranium workers who received X-ray examination later in life. In summary, the results indicate a trend of seasonal changes of individual types of MN and suggest that former exposure can have a protective effect on the level of DNA damage in case of future exposure.
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Affiliation(s)
- Andrea Rossnerova
- Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine, Czech Academy of Sciences, 14220 Prague 4, Czechia.
| | - Katerina Honkova
- Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine, Czech Academy of Sciences, 14220 Prague 4, Czechia
| | - Jitka Pavlikova
- Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine, Czech Academy of Sciences, 14220 Prague 4, Czechia
| | - Zuzana Freitinger Skalicka
- Institute of Radiology, Toxicology and Civil Protection, University of South Bohemia, 37005 Ceske Budejovice, Czechia
| | - Renata Havrankova
- Institute of Radiology, Toxicology and Civil Protection, University of South Bohemia, 37005 Ceske Budejovice, Czechia
| | - Ivo Solansky
- Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine, Czech Academy of Sciences, 14220 Prague 4, Czechia
| | - Pavel Rossner
- Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine, Czech Academy of Sciences, 14220 Prague 4, Czechia
| | - Radim J Sram
- Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine, Czech Academy of Sciences, 14220 Prague 4, Czechia
| | - Friedo Zölzer
- Institute of Radiology, Toxicology and Civil Protection, University of South Bohemia, 37005 Ceske Budejovice, Czechia
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46
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Ambroz A, Vlkova V, Rossner P, Rossnerova A, Svecova V, Milcova A, Pulkrabova J, Hajslova J, Veleminsky M, Solansky I, Sram RJ. Impact of air pollution on oxidative DNA damage and lipid peroxidation in mothers and their newborns. Int J Hyg Environ Health 2016; 219:545-56. [DOI: 10.1016/j.ijheh.2016.05.010] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2016] [Revised: 04/29/2016] [Accepted: 05/30/2016] [Indexed: 01/30/2023]
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Sram RJ, Svecova V, Rossnerova A. Systematic review of the use of the lymphocyte cytokinesis-block micronucleus assay to measure DNA damage induced by exposure to polycyclic aromatic hydrocarbons. MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH 2016; 770:162-169. [PMID: 27894684 DOI: 10.1016/j.mrrev.2016.07.009] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/08/2016] [Revised: 07/26/2016] [Accepted: 07/27/2016] [Indexed: 02/07/2023]
Abstract
The effect of exposure to polycyclic aromatic hydrocarbons (PAHs) to induce micronuclei (MN) measured using the lymphocytes cytokinesis-block micronucleus (CBMN) assay were evaluated in 34 studies according to the exposure: 20 studies in coke oven workers, 7 studies in different occupational exposures as alluminium industry workers, rubber factory workers, road construction workers, airport workers and diesel exposed workers, 6 studies on environmentaly exposed groups as police, volunteers and children. Reviewed papers indicate that the CBMN assay is a sensitive biomarker of PAHs exposure in polluted air. Reviewed studies confirmed previous conclusions, that the frequency of MN measured using the lymphocyte CBMN is not significantly affected by smoking, females are more sensitive to PAHs than males, the frequency of MN is increased with age.
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Affiliation(s)
- Radim J Sram
- Institute of Experimental Medicine AS CR, Prague, Czech Republic.
| | - Vlasta Svecova
- Institute of Experimental Medicine AS CR, Prague, Czech Republic
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48
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Goodrich JM, Reddy P, Naidoo RN, Asharam K, Batterman S, Dolinoy DC. Prenatal exposures and DNA methylation in newborns: a pilot study in Durban, South Africa. ENVIRONMENTAL SCIENCE. PROCESSES & IMPACTS 2016; 18:908-17. [PMID: 27359112 PMCID: PMC4945397 DOI: 10.1039/c6em00074f] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/09/2023]
Abstract
The in utero environment has the potential to influence epigenetic programming and subsequently the health of offspring. Even though pregnant women living in urban Africa are exposed to multiple chemicals and infectious agents that may impact their developing children, the neonatal epigenome has not been studied in these regions. We assessed whether prenatal exposures to air pollution and maternal human immunodeficiency virus (HIV) are associated with changes to DNA methylation throughout the epigenome using a pilot sample from the Mother and Child Environmental (MACE) birth cohort, of which 36% of the mothers are HIV positive. Families living in a high air pollution region (south Durban, n = 11) and a low air pollution region (north Durban, n = 11) with comparable socioeconomic characteristics were selected for analysis. DNA methylation was quantified in cord blood plasma DNA at >430 000 CpG sites using the Infinium HumanMethylation450 BeadChip. Sites associated with living in south Durban or maternal HIV infection (p < 0.001) were more likely to be hypomethylated and located in CpG islands. Top differentially methylated sites by region of Durban were enriched in pathways related to xenobiotic metabolism, oxygen and gas transport, and sensory perception of chemical stimuli when performing gene set enrichment testing with LRpath. Differentially methylated sites by maternal HIV status were enriched in cytochrome P450s, pathways involved in detection of chemical stimuli, metabolic processes, and viral regulation and processing. Given the small sample size of the study, future work examining the impact of prenatal exposures to air pollution, maternal infection, and antiviral treatment on the epigenome and downstream health implications is merited in Sub-Saharan African populations.
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Affiliation(s)
- Jaclyn M Goodrich
- Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109, USA.
| | - Poovendhree Reddy
- Department of Community Health Studies, Durban University of Technology, Durban, South Africa
| | - Rajen N Naidoo
- Discipline of Occupational and Environmental Health, School of Nursing and Public Health, University of KwaZulu-Natal, Durban, South Africa
| | - Kareshma Asharam
- Discipline of Occupational and Environmental Health, School of Nursing and Public Health, University of KwaZulu-Natal, Durban, South Africa
| | - Stuart Batterman
- Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109, USA.
| | - Dana C Dolinoy
- Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109, USA. and Department of Nutritional Sciences, University of Michigan, Ann Arbor, MI, USA
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49
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Clifford RL, Jones MJ, MacIsaac JL, McEwen LM, Goodman SJ, Mostafavi S, Kobor MS, Carlsten C. Inhalation of diesel exhaust and allergen alters human bronchial epithelium DNA methylation. J Allergy Clin Immunol 2016; 139:112-121. [PMID: 27321436 DOI: 10.1016/j.jaci.2016.03.046] [Citation(s) in RCA: 104] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2015] [Revised: 02/15/2016] [Accepted: 03/22/2016] [Indexed: 01/24/2023]
Abstract
BACKGROUND Allergic disease affects 30% to 40% of the world's population, and its development is determined by the interplay between environmental and inherited factors. Air pollution, primarily consisting of diesel exhaust emissions, has increased at a similar rate to allergic disease. Exposure to diesel exhaust may play a role in the development and progression of allergic disease, in particular allergic respiratory disease. One potential mechanism underlying the connection between air pollution and increased allergic disease incidence is DNA methylation, an epigenetic process with the capacity to integrate gene-environment interactions. OBJECTIVE We sought to investigate the effect of allergen and diesel exhaust exposure on bronchial epithelial DNA methylation. METHODS We performed a randomized crossover-controlled exposure study to allergen and diesel exhaust in humans, and measured single-site (CpG) resolution global DNA methylation in bronchial epithelial cells. RESULTS Exposure to allergen alone, diesel exhaust alone, or allergen and diesel exhaust together (coexposure) led to significant changes in 7 CpG sites at 48 hours. However, when the same lung was exposed to allergen and diesel exhaust but separated by approximately 4 weeks, significant changes in more than 500 sites were observed. Furthermore, sites of differential methylation differed depending on which exposure was experienced first. Functional analysis of differentially methylated CpG sites found genes involved in transcription factor activity, protein metabolism, cell adhesion, and vascular development, among others. CONCLUSIONS These findings suggest that specific exposures can prime the lung for changes in DNA methylation induced by a subsequent insult.
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Affiliation(s)
- Rachel L Clifford
- Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
| | - Meaghan J Jones
- Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
| | - Julia L MacIsaac
- Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
| | - Lisa M McEwen
- Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
| | - Sarah J Goodman
- Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
| | - Sara Mostafavi
- Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; Department of Statistics, University of British Columbia, Vancouver, British Columbia, Canada; Canadian Institute for Advanced Research, Toronto, Ontario, Canada
| | - Michael S Kobor
- Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; Canadian Institute for Advanced Research, Toronto, Ontario, Canada; Human Early Learning Partnership, School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Chris Carlsten
- Air Pollution Exposure Laboratory, Chan-Yeung Centre for Occupational and Environmental Lung Disease, Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
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50
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Castro-Rodríguez JA, Krause BJ, Uauy R, Casanello P. [Epigenetics in allergic diseases and asthma]. ACTA ACUST UNITED AC 2016; 87:88-95. [PMID: 27055949 DOI: 10.1016/j.rchipe.2016.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2015] [Revised: 02/21/2016] [Accepted: 02/25/2016] [Indexed: 12/26/2022]
Abstract
Allergic diseases and asthma are the result of complex interactions between genetic predisposition and environmental factors. Asthma is one of the most prevalent chronic disease among children. In this article we review some environmental factors like: allergen exposition, tobacco, bacteria, microbial components, diet, obesity and stress, which influences during intrauterine and infancy life in the epigenetic regulation of asthma and allergic diseases. The review has been done in three models: in-vitro, animal and human.
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Affiliation(s)
- José A Castro-Rodríguez
- División de Pediatría, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; Laboratorio de Programación y Epigenética Perinatal, Centro de Investigaciones Médicas, Santiago, Chile.
| | - Bernardo J Krause
- Laboratorio de Programación y Epigenética Perinatal, Centro de Investigaciones Médicas, Santiago, Chile; División de Obstetricia y Ginecología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Ricardo Uauy
- División de Pediatría, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; Laboratorio de Programación y Epigenética Perinatal, Centro de Investigaciones Médicas, Santiago, Chile
| | - Paola Casanello
- División de Pediatría, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; Laboratorio de Programación y Epigenética Perinatal, Centro de Investigaciones Médicas, Santiago, Chile; División de Obstetricia y Ginecología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
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