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Trevisano RG, Matias H, de Jesus Teani T, Silvino VO, Ferreira CP, Dos Santos MAP, Braga PLG, Almeida SS. The frequency of the ACE I/D polymorphism in South America: a systematic review and meta-analysis. Mol Cell Biochem 2024; 479:2955-2972. [PMID: 38310174 DOI: 10.1007/s11010-023-04923-9] [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: 08/02/2023] [Accepted: 12/26/2023] [Indexed: 02/05/2024]
Abstract
Angiotensin-converting enzyme (ACE) is a key component of the renin-angiotensin system and plays an important role in homeostasis and maintenance of blood pressure. However, little is known about allele and genotypic frequencies, as well as phenotypic characteristics associated with ACE polymorphism genotypes in South American populations. This study aimed to verify the allelic predominance and genotype frequency of ACE I/D polymorphism in South America and its association with the main diseases and related conditions. We conducted a systematic review considering studies published in the last 25 years available in PubMed, Scielo, LILACS, LIPECS, Coleciona SUS, CUMED, BINACIS, IBECS, and MEDLINE databases, resulting in the inclusion of 121 studies. Quality of the studies was assessed according to the Strengthening the Reporting of Genetic Association (STREGA) guidelines. We mapped the frequency of the ACE I/D polymorphism in South American populations. 8,856 (32.1%) subjects were DD, 13,050 were ID (47.4%), and 5,644 were II (20.5%) carriers. The main associated conditions included systemic arterial hypertension and other cardiovascular conditions, cardiorespiratory or respiratory characteristics, physical activity level, kidney conditions, aging-related diseases, as well as different types of cancers and metabolic conditions. 61.1% of the studies found no significant association between the respective conditions investigated and the ACE I/D polymorphism. Considering DD genotype or D allele, 21.5% of the studies observed negative and 4.9% positive outcomes. Regarding ID genotype, 4.1% of the studies identified negative and 0.8% positive outcomes, and for II genotype or I allele, 4.1% of the results had negative and 10.7% positive associations.
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Affiliation(s)
- Rebeca Gonçalves Trevisano
- Department of Obstetrician, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil
| | - Helen Matias
- Department of Obstetrician, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil
| | | | - Valmir Oliveira Silvino
- Department of Biophysics and Physiology, Nucleus of Study in Physiology Applied to Performance and Health (NEFADS), Federal University of Piaui, Teresina, Brazil
- Rede Nordeste de Biotecnologia (RENORBIO) post-graduation program, Teresina, Brazil
| | - Cirley Pinheiro Ferreira
- Department of Biophysics and Physiology, Nucleus of Study in Physiology Applied to Performance and Health (NEFADS), Federal University of Piaui, Teresina, Brazil
- Rede Nordeste de Biotecnologia (RENORBIO) post-graduation program, Teresina, Brazil
| | - Marcos Antonio Pereira Dos Santos
- Department of Biophysics and Physiology, Nucleus of Study in Physiology Applied to Performance and Health (NEFADS), Federal University of Piaui, Teresina, Brazil
- Rede Nordeste de Biotecnologia (RENORBIO) post-graduation program, Teresina, Brazil
| | | | - Sandro Soares Almeida
- Department of Obstetrician, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.
- Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
- Universidade Ibirapuera, São Paulo, SP, Brazil.
- Faculdade Anhanguera de Guarulhos, Guarulhos, SP, Brazil.
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Samet M, Yazdi M, Tajamolian M, Beygi M, Sheikhha MH, Hoseini SM. The Effect of Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism on the Severity and Death Rate of COVID-19 in Iranian Patients. Biochem Genet 2024; 62:3568-3585. [PMID: 38145438 DOI: 10.1007/s10528-023-10614-3] [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: 07/24/2023] [Accepted: 11/22/2023] [Indexed: 12/26/2023]
Abstract
The study was designed to assess the association of ACE I/D polymorphism with the severity and prognosis of COVID-19 in the Iranian population. Hence, 186 adult patients were categorized into three clinical groups based on the severity of COVID-19: 1) Outpatients or mildly symptomatic patients as control (n = 71); 2) Hospitalized patients or severe symptomatic cases (n = 53); 3) Inpatients led to ICU/death or critically ill patients needed mechanical ventilation (n = 62). The possible association of ACE I/D polymorphism with the risk of comorbidities and serum level of C-reactive protein was evaluated in two severe cases. The results showed that the frequency of D and I alleles are 69.35% and 30.65%, respectively, in the total population. The analysis of allelic frequencies via Fisher's exact test confirmed significantly higher frequency of D allele in both severe groups than that in the mild one, 78.31% in Hospitalized patients (OR = 2.56; 95% CI 1.46 to 4.46; p-value = 0.0011) and 74.19% in Inpatients led to ICU/death (OR = 2.04; 95% CI = 1.22 to 3.43; p-value = 0.0094) compared to 58.45% in Outpatients. The results of genotype proportions displayed an association between COVID-19 severity and DD genotype. Overall, our findings in Iranian patients supported the undeniable role of the DD genotype in the intensity of the disease, comparable to other populations. Furthermore, there is no definite evidence regarding the protective effect of the I allele in our inquiry.
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Affiliation(s)
- Mohammad Samet
- Departments of Internal Medicine, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
| | - Mehran Yazdi
- Departments of Internal Medicine, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
| | - Masoud Tajamolian
- Medical Genetics Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mahdi Beygi
- Medical Genetics Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mohammad Hasan Sheikhha
- Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
| | - Seyed Mehdi Hoseini
- Abortion Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran.
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Ailioaie LM, Ailioaie C, Litscher G. Infection, Dysbiosis and Inflammation Interplay in the COVID Era in Children. Int J Mol Sci 2023; 24:10874. [PMID: 37446047 PMCID: PMC10342011 DOI: 10.3390/ijms241310874] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 06/19/2023] [Accepted: 06/26/2023] [Indexed: 07/15/2023] Open
Abstract
For over three years, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents has generated repercussions, especially a few weeks after infection, for symptomatic patients who tested positive, for asymptomatic ones, or even just the contacts of an infected person, and evolved from severe forms such as multisystem inflammatory syndrome in children (MIS-C) to multifarious clinical manifestations in long COVID (LC). Referred to under the umbrella term LC, the onset of persistent and highly heterogeneous symptoms such as fatigue, post-exertion malaise, cognitive dysfunction, and others have a major impact on the child's daily quality of life for months. The first aim of this review was to highlight the circumstances of the pathophysiological changes produced by COVID-19 in children and to better understand the hyperinflammation in COVID-19 and how MIS-C, as a life-threatening condition, could have been avoided in some patients. Another goal was to better identify the interplay between infection, dysbiosis, and inflammation at a molecular and cellular level, to better guide scientists, physicians, and pediatricians to advance new lines of medical action to avoid the post-acute sequelae of SARS-CoV-2 infection. The third objective was to identify symptoms and their connection to molecular pathways to recognize LC more easily. The fourth purpose was to connect the triggering factors of LC with related sequelae following acute SARS-CoV-2 injuries to systems and organs, the persistence of the virus, and some of its components in hidden reservoirs, including the gut and the central nervous system. The reactivation of other latent infectious agents in the host's immune environments, the interaction of this virus with the microbiome, immune hyperactivation, and autoimmunity generated by molecular mimicry between viral agents and host proteins, could initiate a targeted and individualized management. New high-tech solutions, molecules, probiotics, and others should be discovered to innovatively solve the interplay between RNA persistent viruses, microbiota, and our immune system.
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Affiliation(s)
- Laura Marinela Ailioaie
- Department of Medical Physics, Alexandru Ioan Cuza University, 11 Carol I Boulevard, 700506 Iasi, Romania; (L.M.A.); (C.A.)
| | - Constantin Ailioaie
- Department of Medical Physics, Alexandru Ioan Cuza University, 11 Carol I Boulevard, 700506 Iasi, Romania; (L.M.A.); (C.A.)
| | - Gerhard Litscher
- President of the International Society for Medical Laser Applications (ISLA Transcontinental), German Vice President of the German–Chinese Research Foundation (DCFG) for TCM, Honorary President of the European Federation of Acupuncture and Moxibustion Societies, 8053 Graz, Austria
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Ghaffarzadeh A, Nemati M, Hassan-Nejhad M, Khadem-Vatani K, Baghal-Sadriforoush S, Bagheri M. Association of angiotensin-converting enzyme gene variations with coronary artery disease in the Iranian population. ARYA ATHEROSCLEROSIS 2023; 19:12-16. [PMID: 38883156 PMCID: PMC11079297 DOI: 10.48305/arya.2022.11869.2692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Accepted: 08/29/2022] [Indexed: 06/18/2024]
Abstract
BACKGROUND The purpose of this study was to identify the angiotensin-converting enzyme (ACE) gene (I/D) variations in CAD patients and healthy controls in an Iranian population (West Azerbaijan province of Iran). METHOD This cross-sectional study included 95 CAD patients and 203 healthy controls. ACE I/D polymorphisms were assessed using PCR, and their frequency was determined. RESULTS There were 298 people, 95 CAD patients, and 203 controls, with an average age of 50.96±3.45 and 51.14±10.20. We discovered that the frequency of the D allele was significantly higher in CAD patients than in controls (P = 0.0009). In contrast, the frequency of the I allele was significantly higher in controls than in CAD patients (P = 0.0009). The D allele carriers genotypes (DD + ID) were more frequent in the CAD patients than in the control group (P = 0.008). The ACE II genotype-state carriers were more common in the control group than in CAD patients (P = 0.008). However, in the case of the ACE ID genotype, no significant differences were not found in the tested groups (P = 0.47). CONCLUSIONS These findings suggest that individuals with the ACE DD genotype are predisposed to CAD, whereas individuals with the ACE II genotype state are protected.
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Affiliation(s)
- Ayda Ghaffarzadeh
- Cellular and Molecular Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran
| | - Mohadeseh Nemati
- Department of Clinical Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Mahsa Hassan-Nejhad
- Cellular and Molecular Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran
| | - Kamal Khadem-Vatani
- Seyyed-al Shohada University Hospital, Urmia University of Medical Sciences, Urmia, Iran
| | - Sahar Baghal-Sadriforoush
- Cellular and Molecular Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran
| | - Morteza Bagheri
- Cellular and Molecular Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran
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Papadopoulos KI, Sutheesophon W, Manipalviratn S, Aw TC. Age and genotype dependent erythropoietin protection in COVID-19. World J Stem Cells 2021; 13:1513-1529. [PMID: 34786155 PMCID: PMC8567454 DOI: 10.4252/wjsc.v13.i10.1513] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 06/23/2021] [Accepted: 09/19/2021] [Indexed: 02/06/2023] Open
Abstract
Erythropoietin (EPO) is the main mediator of erythropoiesis and an important tissue protective hormone that appears to mediate an ancestral neuroprotective innate immune response mechanism at an early age. When the young brain is threatened-prematurity, neonatal hyperbilirubinemia, malaria- EPO is hyper-secreted disproportionately to any concurrent anemic stimuli. Under eons of severe malarial selection pressure, neuroprotective EPO augmenting genetic determinants such as the various hemoglobinopathies, and the angiotensin converting enzyme (ACE) I/D polymorphism, have been positively selected. When malarial and other cerebral threats abate and the young child survives to adulthood, EPO subsides. Sustained high ACE and angiotensin II (Ang II) levels through the ACE D allele in adulthood may then become detrimental as witnessed by epidemiological studies. The ubiquitous renin angiotensin system (RAS) influences the α-klotho/fibroblast growth factor 23 (FGF23) circuitry, and both are interconnected with EPO. Here we propose that at a young age, EPO augmenting genetic determinants through ACE D allele elevated Ang II levels in some or HbE/beta thalassemia in others would increase EPO levels and shield against coronavirus disease 2019, akin to protection from malaria and dengue fever. Human evolution may use ACE2 as a "bait" for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to gain cellular entry in order to trigger an ACE/ACE2 imbalance and stimulate EPO hypersecretion using tissue RAS, uncoupled from hemoglobin levels. In subjects without EPO augmenting genetic determinants at any age, ACE2 binding and internalization upon SARS-CoV-2 entry would trigger an ACE/ACE2 imbalance, and Ang II oversecretion leading to protective EPO stimulation. In children, low nasal ACE2 Levels would beneficially augment this imbalance, especially for those without protective genetic determinants. On the other hand, in predisposed adults with the ACE D allele, ACE/ACE2 imbalance, may lead to uncontrolled RAS overactivity and an Ang II induced proinflammatory state and immune dysregulation, with interleukin 6 (IL-6), plasminogen activator inhibitor, and FGF23 elevations. IL-6 induced EPO suppression, aggravated through co-morbidities such as hypertension, diabetes, obesity, and RAS pharmacological interventions may potentially lead to acute respiratory distress syndrome, cytokine storm and/or autoimmunity. HbE/beta thalassemia carriers would enjoy protection at any age as their EPO stimulation is uncoupled from the RAS system. The timely use of rhEPO, EPO analogs, acetylsalicylic acid, bioactive lipids, or FGF23 antagonists in genetically predisposed individuals may counteract those detrimental effects.
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Affiliation(s)
| | | | - Somjate Manipalviratn
- Department of Reproductive Endocrinology, Jetanin Institute for Assisted Reproduction, Bangkok 10330, Thailand
| | - Tar-Choon Aw
- Department of Laboratory Medicine, Changi General Hospital, Singapore 529889, Singapore
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Combinations of fibrinolytic gene polymorphisms (plasminogen activator inhibitor type 1 4G/5G, factor XIII Val34Leu and angiotensin-converting enzyme I/D) in women with idiopathic infertility. Blood Coagul Fibrinolysis 2021; 32:103-107. [PMID: 33555692 DOI: 10.1097/mbc.0000000000000995] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
During normal pregnancy depressed fibrinolytic system is caused by changes in many factors, which could be influenced by different gene polymorphisms. The aim of this study was to investigate the combination of fibrinolysis-related gene polymorphisms in women with idiopathic infertility. We genotype polymorphisms 4G/5G in plasminogen activator inhibitor type 1 (PAI-1), Val34Leu in factor XIII (FXIII) and I/D in angiotensin-converting enzyme (ACE) gene. The patients group consisted of 83 females with idiopathic infertility, while the control group included 121 females with at least one born child. The alleles and genotypes distributions showed no significant differences between analyzed groups. Although higher frequency of PAI-1 5G5G genotype in patients did not reach statistical significance, 5G5G genotype of PAI-1 in combination with ValVal genotype of FXIII leads to higher risk for infertility (P < 0.05). In addition, when we added ACE I/D polymorphism in analysis, the 4G in PAI-1 and D allele in ACE, showed protective effect in combination with FXIII polymorphism (P < 0.05). The finding that combined homozygosity of 5G of PAI-1, commonly associated with greater fibrinolytic activity and bleeding tendency, in combination with Val genotype of FXIII impose a risk for female idiopathic infertility. The protective effect of alleles 4G (PAI-1) and D (ACE) suggest that different combinations of polymorphisms influencing fibrinolysis could lead to better established hemostatic balance and reproductive success. Further analyses, with larger number of samples, as well as assessment of additional biochemical parameters of fibrinolysis, should be performed to clarify the role of gene polymorphisms on fibrinolysis and consequently their influence on reproductive success.
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Li M, Schifanella L, Larsen PA. Alu retrotransposons and COVID-19 susceptibility and morbidity. Hum Genomics 2021; 15:2. [PMID: 33390179 PMCID: PMC7779329 DOI: 10.1186/s40246-020-00299-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Accepted: 12/14/2020] [Indexed: 12/22/2022] Open
Abstract
SARS-CoV-2 has spread rapidly across the world and is negatively impacting the global human population. COVID-19 patients display a wide variety of symptoms and clinical outcomes, including those attributed to genetic ancestry. Alu retrotransposons have played an important role in human evolution, and their variants influence host response to viral infection. Intronic Alus regulate gene expression through several mechanisms, including both genetic and epigenetic pathways. With respect to SARS-CoV-2, an intronic Alu within the ACE gene is hypothesized to be associated with COVID-19 susceptibility and morbidity. Here, we review specific Alu polymorphisms that are of particular interest when considering host response to SARS-CoV-2 infection, especially polymorphic Alu insertions in genes associated with immune response and coagulation/fibrinolysis cascade. We posit that additional research focused on Alu-related pathways could yield novel biomarkers capable of predicting clinical outcomes as well as patient-specific treatment strategies for COVID-19 and related infectious diseases.
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Affiliation(s)
- Manci Li
- Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN, 55108, USA
| | - Luca Schifanella
- Department of Surgery, Division of Surgical Outcomes and Precision Medicine Research, University of Minnesota Medical School, Minneapolis, MN, 55455, USA
| | - Peter A Larsen
- Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN, 55108, USA.
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Hemostasis-related gene polymorphisms and their epistatic relationship in women with idiopathic infertility. Blood Coagul Fibrinolysis 2019; 30:253-262. [PMID: 31259774 DOI: 10.1097/mbc.0000000000000830] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
: A numerous factor can cause infertility, but around one of four reproductive failure cases remain unexplained and diagnosed as idiopathic infertility. In the past few decades, analysis of gene polymorphisms takes a significant place in pathogenesis of infertility. The aim of this study was to evaluate the possible role of hemostasis-related gene polymorphisms in unexplained infertility. The study includes 117 female patients with idiopathic infertility and 130 fertile women with at least one born child. Eight polymorphisms important for hemostasis (ITGB3 1565T>C, FV 1691G>A, FII 20210G>A, MTHFR 677C>T and 1298A>C, ATIII 786G>A, PAI-14G/5G and ACE I/D) were genotyped by real-time PCR system. The frequencies of alleles and genotypes of examined polymorphisms were analyzed in SPSS statistical program, whereas gene interactions were identified using the GMDR software. Examination of etiological factors has shown that family history is a significant factor in assessing individual risk for infertility. The alleles and genotypes frequency of FV 1691G>A and FII 20210G>A polymorphisms were statistically different between control and patient group leading to a greater risk for infertility. The analysis of epistatic relationship between examined hemostasis-related gene polymorphisms identified more complex high-risk genotypes associated with infertility. Our results suggest that positive family history could be important predictive factor for fertility problems, pointing to the potential hereditary basis of this condition. Polymorphisms FVL and FII prothrombin are independent risk factors for idiopathic infertility, whereas multilocus interactions approach should be taken into consideration for the future research.
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Hočevar K, Peterlin A, Jovanović AM, Božović A, Ristanović M, Tul N, Peterlin B. Association between angiotensin-converting enzyme gene insertion/deletion polymorphism and susceptibility to preterm birth: A case-control study and meta-analysis. Eur J Obstet Gynecol Reprod Biol 2018; 231:122-128. [PMID: 30366344 DOI: 10.1016/j.ejogrb.2018.09.019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Revised: 08/01/2018] [Accepted: 09/10/2018] [Indexed: 10/28/2022]
Abstract
BACKGROUND Preterm birth is the largest contributor to newborn mortality, morbidity, and hospitalization in the first year of life worldwide. Previous studies have suggested the importance of genetic variation in the angiotensin-converting enzyme gene, including the angiotensin-converting enzyme gene insertion/deletion polymorphism, in association with preterm birth. The angiotensin-converting enzyme is a key component of the renin-angiotensin system that is involved in blood pressure homeostasis during pregnancy and also affects risk factors of preterm birth, including the regulation of fibrinolytic system, uteroplacental circulation, vascularization of the placenta, and inflammation. OBJECTIVE The results of previous studies investigating the association between the insertion/deletion polymorphism and susceptibility to preterm birth have been inconsistent, therefore, we have performed a case-control study and conducted a meta-analysis of related studies to clarify this association. STUDY DESIGN In a case-control genetic association study, performed on 217 women with a history of preterm birth and 158 women who experienced full-term pregnancy, the significances of associations between allelic and genotype frequencies and preterm birth were determined using Chi-square tests. Following the case-control study, PubMed, Scopus, Google Scholar, and HugeNavigator databases were systematically searched to identify relevant studies. Altogether, four eligible studies involving 369 cases and 559 controls were included in the meta-analysis. The strength of the association between the angiotensin-converting enzyme gene insertion/deletion polymorphism for preterm birth was estimated by odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs), using a fixed-effects model (Mantel-Haenszel method). RESULTS In our case-control study we did not detect a significant association of angiotensin-converting enzyme insertion/deletion alleles and genotypes with preterm birth. The results of the meta-analysis showed a significant association between the angiotensin-converting enzyme gene insertion/deletion and the risk of preterm birth under allelic, dominant, and recessive comparison genetic models (D vs. I: OR = 1.35, 95% CI = 1.11-1.65, p = 0.0033; DD + ID vs. II: OR = 1.52, 95% CI = 1.08-2.15, p = 0.0161; DD vs. ID + II: OR = 1.48, 95% CI = 1.07-2.04, p = 0.0184). CONCLUSIONS The present meta-analysis suggests that the insertion/deletion polymorphism of the angiotensin-converting enzyme gene in mothers might be associated with preterm birth, however, further well-designed large replication studies involving various ethnicities are needed to confirm this association.
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Affiliation(s)
- Keli Hočevar
- Clinical Institute of Medical Genetics, University Medical Centre Ljubljana, Ljubljana, Slovenia
| | - Ana Peterlin
- Clinical Institute of Medical Genetics, University Medical Centre Ljubljana, Ljubljana, Slovenia
| | | | | | - Momčilo Ristanović
- Institute of Human Genetics, Medical Faculty, University of Belgrade, Belgrade, Serbia
| | - Nataša Tul
- Department of Perinatology, Division of Obstetrics and Gynaecology, University Medical Centre Ljubljana, Ljubljana, Slovenia
| | - Borut Peterlin
- Clinical Institute of Medical Genetics, University Medical Centre Ljubljana, Ljubljana, Slovenia.
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Fenwick PH, Jeejeebhoy K, Dhaliwal R, Royall D, Brauer P, Tremblay A, Klein D, Mutch DM. Lifestyle genomics and the metabolic syndrome: A review of genetic variants that influence response to diet and exercise interventions. Crit Rev Food Sci Nutr 2018; 59:2028-2039. [PMID: 29400991 DOI: 10.1080/10408398.2018.1437022] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Metabolic syndrome (MetS) comprises a cluster of risk factors that includes central obesity, dyslipidemia, impaired glucose homeostasis and hypertension. Individuals with MetS have elevated risk of type 2 diabetes and cardiovascular disease; thus placing significant burdens on social and healthcare systems. Lifestyle interventions (comprised of diet, exercise or a combination of both) are routinely recommended as the first line of treatment for MetS. Only a proportion of people respond, and it has been assumed that psychological and social aspects primarily account for these differences. However, the etiology of MetS is multifactorial and stems, in part, on a person's genetic make-up. Numerous single nucleotide polymorphisms (SNPs) are associated with the various components of MetS, and several of these SNPs have been shown to modify a person's response to lifestyle interventions. Consequently, genetic variants can influence the extent to which a person responds to changes in diet and/or exercise. The goal of this review is to highlight SNPs reported to influence the magnitude of change in body weight, dyslipidemia, glucose homeostasis and blood pressure during lifestyle interventions aimed at improving MetS components. Knowledge regarding these genetic variants and their ability to modulate a person's response will provide additional context for improving the effectiveness of personalized lifestyle interventions that aim to reduce the risks associated with MetS.
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Affiliation(s)
- Peri H Fenwick
- a Department of Human Health and Nutritional Sciences , University of Guelph , Guelph , Ontario , Canada
| | - Khursheed Jeejeebhoy
- b Emeritus Professor of Medicine and Physician , St. Michael's Hospital , Toronto , Ontario , Canada
| | | | - Dawna Royall
- d Department of Family Relations and Applied Nutrition , University of Guelph , Guelph , Ontario , Canada
| | - Paula Brauer
- d Department of Family Relations and Applied Nutrition , University of Guelph , Guelph , Ontario , Canada
| | - Angelo Tremblay
- e Department of Kinesiology , Faculty of Medicine, Université Laval , Québec City , Québec , Canada
| | - Doug Klein
- f Department of Family Medicine , University of Alberta , Edmonton , Alberta , Canada
| | - David M Mutch
- a Department of Human Health and Nutritional Sciences , University of Guelph , Guelph , Ontario , Canada
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D'Elia JA, Bayliss G, Gleason RE, Weinrauch LA. Cardiovascular-renal complications and the possible role of plasminogen activator inhibitor: a review. Clin Kidney J 2016; 9:705-12. [PMID: 27679717 PMCID: PMC5036907 DOI: 10.1093/ckj/sfw080] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2015] [Accepted: 07/20/2016] [Indexed: 12/14/2022] Open
Abstract
Since angiotensin increases the expression of plasminogen activator inhibitor (PAI), mechanisms associated with an actively functioning renin–angiotensin–aldosterone system can be expected to be associated with increased PAI-1 expression. These mechanisms are present not only in common conditions resulting in glomerulosclerosis associated with aging, diabetes or genetic mutations, but also in autoimmune disease (like scleroderma and lupus), radiation injury, cyclosporine toxicity, allograft nephropathy and ureteral obstruction. While the renin–angiotensin–aldosterone system and growth factors, such as transforming growth factor-beta (TGF-β), are almost always part of the process, there are rare experimental observations of PAI-1 expression without their interaction. Here we review the literature on PAI-1 and its role in vascular, fibrotic and oxidative injury as well as work suggesting potential areas of intervention in the pathogenesis of multiple disorders.
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Affiliation(s)
- John A D'Elia
- Joslin Diabetes Center, Boston, MA, USA; Beth Israel Deaconess Medical Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
| | - George Bayliss
- Division ofKidney Diseases and Hypertension, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA; The Miriam Hospital, Providence, RI, USA; Alpert Medical School, Brown University, Providence, RI, USA
| | - Ray E Gleason
- Joslin Diabetes Center, Boston, MA, USA; Beth Israel Deaconess Medical Center, Boston, MA, USA; EP Joslin Research Laboratory, Boston, MA, USA; Brigham and Women's Hospital, Boston, MA, USA
| | - Larry A Weinrauch
- Joslin Diabetes Center, Boston, MA, USA; Beth Israel Deaconess Medical Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; EP Joslin Research Laboratory, Boston, MA, USA; Brigham and Women's Hospital, Boston, MA, USA
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