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Hejtmancik JF. Oxidative Stress in Genetic Cataract Formation. Antioxidants (Basel) 2024; 13:1315. [PMID: 39594457 PMCID: PMC11591473 DOI: 10.3390/antiox13111315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 10/22/2024] [Accepted: 10/25/2024] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND Cataracts are the leading cause of blindness worldwide, and age-related cataracts are the result of environmental insults that largely lead to oxidative stress imposed on a genetic background that determines susceptibility to these stresses. METHODS A comprehensive literature review was performed to identify GWAS, targeted association studies, and TWAS that identified genes associated with age-related cataract. Additional genes associated with age-related cataracts were identified through the CAT-MAP online database. Pathway analysis was performed using Qiagen Ingenuity Pathway Analysis and pathways related to oxidative stress were analyzed using the same program. RESULTS A large number of genes have been identified as causes of both Mendelian and complex cataracts. Of these, 10 genes related to oxidative stress were identified, and all were associated with age-related cataracts. These genes fall into seven canonical pathways primarily related to glutathione metabolism and other pathways related to detoxifying reactive oxygen species. CONCLUSIONS While a relatively small number of antioxidant related genes were identified as being associated with cataracts, they allow the identification of redox pathways important for lens metabolism and homeostasis. These are largely related to glutathione and its metabolism, other pathways for detoxification of reactive oxygen species, and the transcriptional systems that control their expression.
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Affiliation(s)
- James Fielding Hejtmancik
- Ophthalmic Molecular Genetics Section, Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
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Nakanishi G, Pita-Oliveira M, Bertagnolli LS, Torres-Loureiro S, Scudeler MM, Cirino HS, Chaves ML, Miwa B, Rodrigues-Soares F. Worldwide Systematic Review of GSTM1 and GSTT1 Null Genotypes by Continent, Ethnicity, and Therapeutic Area. OMICS : A JOURNAL OF INTEGRATIVE BIOLOGY 2022; 26:528-541. [PMID: 36112350 DOI: 10.1089/omi.2022.0090] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Glutathione S-transferase Mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1) enzymes are glutathione-S-transferases with broad significance for susceptibility or resistance to multifactorial human diseases, as well as detoxification of environmental chemicals and drugs. Moreover, some individuals may have a complete deletion of GSTM1 and GSTT1 genes, which can contribute to patient-to-patient variability in drug safety and efficacy. GSTM1 and GSTT1 gene deletion frequencies can vary according to ethnicity and continental origin of the studied population with implications for achieving the goal of precision/personalized medicine in clinical practice. We report here a worldwide systematic review of the null genotypes in these two clinically important genes by continents, ethnicities, and therapeutic areas (TAs). Searches were performed in the PubMed database covering the period from 1992 to 2020. Out of the 1925 articles included, most studies analyzed European individuals, corroborating the literature failure for not adequately considering the non-European ethnicities. The frequency of GSTM1 and GSTT1 null genotypes was higher in patients than in healthy volunteers. Conversely, in East Asians, higher frequencies of the null genotypes were observed in healthy volunteers than patients. Oncology was the most intensively studied TA (57% of the articles) in relation to GSTM1 and GSTT1. In all, these results demonstrate that there is an important gap in the literature in terms of failure to consider a broader range of populations, as well as diseases wherein GSTM1 and GSTT1 variations have clinical and biological implications. To achieve precision/personalized medicine on a global/worldwide scale, with equity and inclusiveness, this knowledge/research gap ought to be remedied in studies of GSTM1 and GSTT1 null genotypes. To the best of our knowledge, this is the largest systematic review conducted to date addressing the GSTM1 and GSTT1 null genotypes worldwide. The analyses from the 1925 articles highlighted the current knowledge gaps in different TAs, ethnicities, and populations. Filling these gaps is of importance, given the role these genes play in relation to the metabolism of substances to which we have frequent contact with, the associations observed between their deletion and diseases such as cancer, in addition to the interethnic differences observed for the deletion frequencies of these genes.
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Affiliation(s)
- Giovana Nakanishi
- Departamento de Patologia, Genética e Evolução, Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, Uberaba, Brazil
| | - Murilo Pita-Oliveira
- Departamento de Patologia, Genética e Evolução, Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, Uberaba, Brazil
| | - Laísa S Bertagnolli
- Departamento de Patologia, Genética e Evolução, Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, Uberaba, Brazil
| | - Sabrina Torres-Loureiro
- Departamento de Patologia, Genética e Evolução, Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, Uberaba, Brazil
| | - Mariana M Scudeler
- Departamento de Patologia, Genética e Evolução, Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, Uberaba, Brazil
| | - Heithor S Cirino
- Departamento de Patologia, Genética e Evolução, Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, Uberaba, Brazil
| | - Maria Laura Chaves
- Departamento de Patologia, Genética e Evolução, Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, Uberaba, Brazil
| | - Bruno Miwa
- Departamento de Patologia, Genética e Evolução, Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, Uberaba, Brazil
| | - Fernanda Rodrigues-Soares
- Departamento de Patologia, Genética e Evolução, Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, Uberaba, Brazil
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Chen X, Luo Y. Association of GSTM1, GSTT1, and GSTP1 Ile105Val polymorphisms with risk of age-related macular degeneration: a meta-analysis. Ophthalmic Genet 2022; 43:615-621. [PMID: 35730167 DOI: 10.1080/13816810.2022.2090009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
BACKGROUND This study determined to evaluate the association between glutathione S-transferase (GST) polymorphisms, namely, GSTM1 (rs1183423000, presence/absence), GSTT1 (rs1601993659, presence/absence), and GSTP1 Ile105Val (rs1695, A>G) polymorphisms, and AMD risk. METHODS We searched PubMed, Embase, and Web of Science databases from January 2000 to June 2021. The odds ratio (OR) and 95% confidence interval (95% CI) were used as effect sizes. Heterogeneity was assessed using the heterogeneity metric I2. RESULTS Five relevant studies involving 875 patients with AMD and 966 healthy controls were included in this meta-analysis, four studies concerning GSTM1 null polymorphism, four studies regarding GSTT1 null polymorphism, and four studies on GSTP1 Ile105Val polymorphism. The GSTM1 null polymorphism, GSTT1 null polymorphism and GSTP1 Ile105Val polymorphism were not significantly associated with AMD risk (OR 1.13, 95% CI 0.73-1.75, p = 0.59; OR 1.05, 95% CI 0.81-1.36, p = 0.69; OR 1.20, 95% CI 0.97-1.47, p = 0.09, respectively). There was no association between the combined GSTM1 null genotype and GSTT1 null genotype and AMD risk (OR 1.16, 95% CI 0.42-3.17, p = 0.77). Subgroup analyses revealed that the GSTM1 null genotype was associated with an increased risk of AMD in the Turkish population (OR 1.67, 95% CI 1.13-2.47, p = 0.01) and the GSTM1 null genotype was associated with a decreased incidence of non-exudative AMD (OR 0.72, 95% CI 0.52-0.99, p = 0.01). There was no obvious risk of publication bias found. CONCLUSIONS This meta-analysis indicated that there were no significant associations between GSTM1, GSTT1, and GSTP1 Ile105Val polymorphisms and AMD risk.
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Affiliation(s)
- Xiaodong Chen
- Department of Ophthalmology and Optometry, Nanchang University, Nanchang, Jiangxi Province, China
| | - Yunfeng Luo
- Jiangxi Research Institute of Ophthalmology and Visual Sciences, Jiangxi Clinical Research Center for Ophthalmic Disease, Jiangxi Provincial Key Laboratory for Ophthalmology, Affiliated Eye Hospital of Nanchang University, Nanchang, Jiangxi, China
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Karimian M, Parvaresh L, Behjati M. Genetic variations as molecular diagnostic factors for idiopathic male infertility: current knowledge and future perspectives. Expert Rev Mol Diagn 2021; 21:1191-1210. [PMID: 34555965 DOI: 10.1080/14737159.2021.1985469] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
INTRODUCTION Infertility is a major health problem, worldwide, which affects 10-15% of couples. About half a percent of infertility cases are related to male-related factors. Male infertility is a complex disease that is the result of various insults as lifestyle issues, genetics, and epigenetic factors. Idiopathic infertility is responsible for 30% of total cases. The genetic factors responsible for male infertility include chromosomal abnormalities, deletions of chromosome Y, and mutations and genetic variations of key genes. AREAS COVERED In this review article, we aim to narrate performed studies on polymorphisms of essential genes involved in male infertility including folate metabolizing genes, oxidative stress-related genes, inflammation, and cellular pathways related to spermatogenesis. Moreover, possible pathophysiologic mechanisms responsible for genetic polymorphisms are discussed. EXPERT OPINION Analysis and assessment of these genetic variations could help in screening, diagnosis, and treatment of idiopathic male infertility.
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Affiliation(s)
- Mohammad Karimian
- Department of Molecular and Cell Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Iran
| | - Leila Parvaresh
- Department of Anatomy, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohaddeseh Behjati
- Cellular, Molecular and Genetics Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
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Shiels A, Hejtmancik JF. Inherited cataracts: Genetic mechanisms and pathways new and old. Exp Eye Res 2021; 209:108662. [PMID: 34126080 PMCID: PMC8595562 DOI: 10.1016/j.exer.2021.108662] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 05/13/2021] [Accepted: 06/01/2021] [Indexed: 12/15/2022]
Abstract
Cataract(s) is the clinical equivalent of lens opacity and is caused by light scattering either by high molecular weight protein aggregates in lens cells or disruption of the lens microarchitecture itself. Genetic mutations underlying inherited cataract can provide insight into the biological processes and pathways critical for lens homeostasis and transparency, classically including the lens crystallins, connexins, membrane proteins or components, and intermediate filament proteins. More recently, cataract genes have been expanded to include newly identified biological processes such as chaperone or protein degradation components, transcription or growth factors, channels active in the lens circulation, and collagen and extracellular matrix components. Cataracts can be classified by age, and in general congenital cataracts are caused by severe mutations resulting in major damage to lens proteins, while age related cataracts are associated with variants that merely destabilize proteins thereby increasing susceptibility to environmental insults over time. Thus there might be separate pathways to opacity for congenital and age-related cataracts whereby congenital cataracts induce the unfolded protein response (UPR) and apoptosis to destroy the lens microarchitecture, while in age related cataract high molecular weight (HMW) aggregates formed by denatured crystallins bound by α-crystallin result in light scattering without severe damage to the lens microarchitecture.
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Affiliation(s)
- Alan Shiels
- Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, 63110, USA.
| | - J Fielding Hejtmancik
- Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892-1860, USA.
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Jiang H, Gao Y, Chen Z, Xu H. Association between MMP-2 gene polymorphism and cataract susceptibility: A protocol for systematic review and meta-analysis. Medicine (Baltimore) 2021; 100:e25392. [PMID: 33832130 PMCID: PMC8036040 DOI: 10.1097/md.0000000000025392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Accepted: 03/14/2021] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Matrix metalloproteinase-2 (MMP-2) polymorphisms have been considered as risk factors of cataracts, but the results still remain controversial. In this study, we have performed a systematic meta-analysis to evaluate the association between MMP-2 polymorphisms and cataract risks. METHODS Published literature was retrieved from Wanfang, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chongqing VIP Chinese Science and Technology Periodical Database, PubMed, Embase, and Web of Science databases. The case-control studies that explored the association between MMP-2 polymorphisms and cataract risks were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random- or fixed-effects model. RESULTS This study could provide high-quality and evidence-based medical evidence for the correlation between MMP-2 polymorphisms and cataract risks. CONCLUSION The study could provide updated evidence for the evaluation of the relationship between MMP-2 polymorphism and cataract risk. ETHICS AND DISSEMINATION The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER DOI 10.17605/OSF.IO/KU9NE.
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Abstract
Cataract, the clinical correlate of opacity or light scattering in the eye lens, is usually caused by the presence of high-molecular-weight (HMW) protein aggregates or disruption of the lens microarchitecture. In general, genes involved in inherited cataracts reflect important processes and pathways in the lens including lens crystallins, connexins, growth factors, membrane proteins, intermediate filament proteins, and chaperones. Usually, mutations causing severe damage to proteins cause congenital cataracts, while milder variants increasing susceptibility to environmental insults are associated with age-related cataracts. These may have different pathogenic mechanisms: Congenital cataracts induce the unfolded protein response and apoptosis. By contrast, denatured crystallins in age-related cataracts are bound by α-crystallin and form light-scattering HMW aggregates. New therapeutic approaches to age-related cataracts use chemical chaperones to solubilize HMW aggregates, while attempts are being made to regenerate lenses using endogenous stem cells to treat congenital cataracts.
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Affiliation(s)
- Alan Shiels
- Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA;
| | - J Fielding Hejtmancik
- Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-1860, USA;
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Ghorbel R, Ben Salah G, Ghorbel R, Ben Mahmoud A, Chamkha I, Mkaouar-Rebai E, Ammar-Keskes L, Fakhfakh F. Do GSTM1 and GSTT1 polymorphisms influence the risk of developing mitochondrial diseases in a Tunisian population? ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2018; 25:5779-5787. [PMID: 29235020 DOI: 10.1007/s11356-017-0775-7] [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: 09/04/2017] [Accepted: 11/15/2017] [Indexed: 06/07/2023]
Abstract
Mitochondria play an essential role to supply the cell with metabolic energy in the form of adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). As a consequence, they are also the primary source of cellular reactive oxygen species (ROS) which can cause oxidative damage of individual respiratory chain complexes. Indeed, affected OXPHOS subunits result in decreases in ATP production and increases in ROS formation which generate oxidative phosphorylation deficiency leading to mitochondrial dysfunctions. It has been suggested that ROS play a vital role in the pathogenesis of mitochondrial diseases. To the best of our knowledge, this is the first study which aimed to investigate the genetic variant effect of the antioxidant enzymes GSTM1 and GSTT1 on mitochondrial disease among a Tunisian population. In this report, 109 patients with mitochondrial disease and 154 healthy controls were genotyped by multiplex PCR amplification, and data were analyzed by SPSS v20 software. The results showed that GSTM1 null genotype was found to be associated with mitochondrial disease with a protective effect; however, no significant association of GSTT1 polymorphism with mitochondrial disease risk was revealed. But, interestingly, our findings highlight that GSTM1 active and GSTT1 null genotype combination increased by three fold the risk of developing mitochondrial disease with p c = 0.020, notably mitochondrial myopathy with p c = 0.046 and Leigh syndrome with p c = 0.042. In conclusion, this study suggests that GSTM1 active and GSTT1 null genotype combination might be a risk factor in developing mitochondrial disease.
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Affiliation(s)
- Raouia Ghorbel
- Laboratory of Human Molecular Genetics, Faculty of Medicine of Sfax, University of Sfax, Sfax, Tunisia.
| | - Ghada Ben Salah
- Unaizah Pharmacy College, Qassim University, Al-Qassim, Saudi Arabia
| | - Rania Ghorbel
- Laboratory of Human Molecular Genetics, Faculty of Medicine of Sfax, University of Sfax, Sfax, Tunisia
| | - Afif Ben Mahmoud
- Laboratory of Human Molecular Genetics, Faculty of Medicine of Sfax, University of Sfax, Sfax, Tunisia
| | - Imen Chamkha
- Department of Mitochondrial Medicine, Lund University, Lund, Sweden
| | - Emna Mkaouar-Rebai
- Laboratory of Molecular and Functional Genetics, Faculty of Sciences of Sfax, University of Sfax, Sfax, Tunisia
| | - Leila Ammar-Keskes
- Laboratory of Human Molecular Genetics, Faculty of Medicine of Sfax, University of Sfax, Sfax, Tunisia
| | - Faiza Fakhfakh
- Laboratory of Molecular and Functional Genetics, Faculty of Sciences of Sfax, University of Sfax, Sfax, Tunisia
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Patel R, Zenith RK, Chandra A, Ali A. Novel Mutations in the Crystallin Gene in Age-Related Cataract Patients from a North Indian Population. Mol Syndromol 2017; 8:179-186. [PMID: 28690483 DOI: 10.1159/000471992] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/13/2017] [Indexed: 12/17/2022] Open
Abstract
Cataract is the most prevalent leading cause of visual impairment and blindness worldwide. In comparison to congenital cataract, which affects relatively few individuals, age-related cataract is responsible for slightly half of all cases of blindness worldwide. Although significant work has been done, the genetic aspect of age-related cataract is still in its infancy. The current study was performed to analyze the mutations and polymorphisms in the CRYAA, CRYAB, CRYBB1, and GJA8 genes in 40 unrelated age-related cataract patients. Mutational analysis of the above-mentioned genes in 40 cataract cases revealed 14 different substitutions of which 8 variants were novel and 6 were reported SNPs. Two disease-causing mutations, g.44590631G>A (p.R65Q) and g.44592224G>A (p.R119H), were also observed in the CRYAA gene. The disease-causing variants mildly affect the stability, functionality, and localization of crystallin, and, with progressing age, a small change in the microenvironment of the crystallin lens occurs. This change in combination with a mutation may significantly alter the functionality of the crystallin protein, leading to age-related cataract.
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Affiliation(s)
- Rashmi Patel
- Centre for Genetic Disorders, Institute of Science, Banaras Hindu University, Varanasi, India
| | - Ravish K Zenith
- Department of Ophthalmology, Sir Sunderlal Hospital, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
| | | | - Akhtar Ali
- Centre for Genetic Disorders, Institute of Science, Banaras Hindu University, Varanasi, India
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Wu X, Lai W, Lin H, Liu Y. Association of OGG1 and MTHFR polymorphisms with age-related cataract: A systematic review and meta-analysis. PLoS One 2017; 12:e0172092. [PMID: 28253266 PMCID: PMC5333819 DOI: 10.1371/journal.pone.0172092] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2016] [Accepted: 01/15/2017] [Indexed: 01/19/2023] Open
Abstract
PURPOSE To discern and confirm genetic biomarkers that help identify populations at high risk for age-related cataract (ARC). METHODS A literature search was performed in the PubMed, Web of Science and China National Knowledge Internet databases for genetic association studies published before June 26, 2016 regarding ARC susceptibility. All genetic polymorphisms reported were systematically reviewed, followed by extraction of candidate genes/loci with sufficient genotype data in ≥3 studies for the meta-analysis. A random/fixed-effects model was used to calculate the pooled odds ratios and 95% confidence intervals to evaluate the associations considering multiple genetic models. Sensitivity analysis was also performed. RESULTS A total of 144 polymorphisms in 36 genes were reported in the 61 previous genetic association studies. Thereby, three polymorphisms of two genes (8-oxoguanine DNA glycosylase-1 [OGG1]; methylenetetrahydrofolate reductase NADPH [MTHFR]) in eight studies were included in the meta-analysis. Regarding the OGG1-rs1052133, the GG (OR = 1.925; 95%CI, 1.181-3.136; p = 0.009) and CG (OR = 1.384; 95%CI, 1.171-1.636; p<0.001) genotypes indicated higher risk of ARC. For the MTHFR gene, the CC+TT genotype of rs1801133 might be protective (OR, 0.838; 95%CI, 0.710-0.989; p = 0.036), whereas the AA+CC genotype of rs1801131 indicated increased risk for the mixed subtype (OR = 1.517; 95%CI, 1.113-2.067; p = 0.008). CONCLUSIONS Polymorphisms of OGG1 and MTHFR genes are associated with ARC susceptibility and may help identify populations at high risk for ARC.
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Affiliation(s)
- Xiaohang Wu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Weiyi Lai
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Haotian Lin
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China
- * E-mail: (HL); (YL)
| | - Yizhi Liu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China
- * E-mail: (HL); (YL)
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Shiels A, Hejtmancik JF. Mutations and mechanisms in congenital and age-related cataracts. Exp Eye Res 2017; 156:95-102. [PMID: 27334249 PMCID: PMC5538314 DOI: 10.1016/j.exer.2016.06.011] [Citation(s) in RCA: 152] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2015] [Revised: 06/09/2016] [Accepted: 06/16/2016] [Indexed: 01/06/2023]
Abstract
The crystalline lens plays an important role in the refractive vision of vertebrates by facilitating variable fine focusing of light onto the retina. Loss of lens transparency, or cataract, is a frequently acquired cause of visual impairment in adults and may also present during childhood. Genetic studies have identified mutations in over 30 causative genes for congenital or other early-onset forms of cataract as well as several gene variants associated with age-related cataract. However, the pathogenic mechanisms resulting from genetic determinants of cataract are only just beginning to be understood. Here, we briefly summarize current concepts pointing to differences in the molecular mechanisms underlying congenital and age-related forms of cataract.
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Affiliation(s)
- Alan Shiels
- Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - J Fielding Hejtmancik
- Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1860, USA.
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Chen J, Zhou J, Wu J, Zhang G, Kang L, Ben J, Wang Y, Qin B, Guan H. Aberrant Epigenetic Alterations of Glutathione-S-Transferase P1 in Age-Related Nuclear Cataract. Curr Eye Res 2016; 42:402-410. [PMID: 27348130 DOI: 10.1080/02713683.2016.1185129] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Affiliation(s)
- Jia Chen
- Eye Institute, Affiliated Hospital of Nantong University, Nantong, China
| | - Jing Zhou
- Eye Institute, Affiliated Hospital of Nantong University, Nantong, China
| | - Jian Wu
- Eye Institute, Affiliated Hospital of Nantong University, Nantong, China
| | - Guowei Zhang
- Eye Institute, Affiliated Hospital of Nantong University, Nantong, China
| | - Lihua Kang
- Eye Institute, Affiliated Hospital of Nantong University, Nantong, China
| | - Jindong Ben
- Eye Institute, Affiliated Hospital of Nantong University, Nantong, China
| | - Yong Wang
- Eye Institute, Affiliated Hospital of Nantong University, Nantong, China
| | - Bai Qin
- Eye Institute, Affiliated Hospital of Nantong University, Nantong, China
| | - Huaijin Guan
- Eye Institute, Affiliated Hospital of Nantong University, Nantong, China
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Mathew S, Abdel-Hafiz H, Raza A, Fatima K, Qadri I. Host nucleotide polymorphism in hepatitis B virus-associated hepatocellular carcinoma. World J Hepatol 2016; 8:485-498. [PMID: 27057306 PMCID: PMC4820640 DOI: 10.4254/wjh.v8.i10.485] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2015] [Revised: 12/04/2015] [Accepted: 03/07/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is etiologically linked with hepatitis B virus (HBV) and is the leading cause of death amongst 80% of HBV patients. Among HBV affected patients, genetic factors are also involved in modifying the risk factors of HCC. However, the genetic factors that regulate progression to HCC still remain to be determined. In this review, we discuss several single nucleotide polymorphisms (SNPs) which were reportedly associated with increased or reduced risk of HCC occurrence in patients with chronic HBV infection such as cyclooxygenase (COX)-2 expression specifically at COX-2 -1195G/A in Chinese, Turkish and Egyptian populations, tumor necrosis factor α and the three most commonly studied SNPs: PAT-/+, Lys939Gln (A33512C, rs2228001) and Ala499Val (C21151T, rs2228000). In genome-wide association studies, strong associations have also been found at loci 1p36.22, 11q22.3, 6p21 (rs1419881, rs3997872, rs7453920 and rs7768538), 8p12 (rs2275959 and rs37821974) and 22q11.21. The genes implicated in these studies include HLA-DQB2, HLA-DQA1, TCF19, HLA-C, UBE2L3, LTL, FDX1, MICA, UBE4B and PG. The SNPs found to be associated with the above-mentioned genes still require validation in association studies in order to be considered good prognostic candidates for HCC. Screening of these polymorphisms is very beneficial in clinical experiments to stratify the higher or lower risk for HCC and may help in designing effective and efficient HCC surveillance programs for chronic HBV-infected patients if further genetic vulnerabilities are detected.
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Affiliation(s)
- Shilu Mathew
- Shilu Mathew, Center of Excellence in Genomic Medicine Research, King Abdul Aziz University, Jeddah 21589, Saudi Arabia
| | - Hany Abdel-Hafiz
- Shilu Mathew, Center of Excellence in Genomic Medicine Research, King Abdul Aziz University, Jeddah 21589, Saudi Arabia
| | - Abbas Raza
- Shilu Mathew, Center of Excellence in Genomic Medicine Research, King Abdul Aziz University, Jeddah 21589, Saudi Arabia
| | - Kaneez Fatima
- Shilu Mathew, Center of Excellence in Genomic Medicine Research, King Abdul Aziz University, Jeddah 21589, Saudi Arabia
| | - Ishtiaq Qadri
- Shilu Mathew, Center of Excellence in Genomic Medicine Research, King Abdul Aziz University, Jeddah 21589, Saudi Arabia
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Hamada N, Fujimichi Y. Role of carcinogenesis related mechanisms in cataractogenesis and its implications for ionizing radiation cataractogenesis. Cancer Lett 2015; 368:262-74. [DOI: 10.1016/j.canlet.2015.02.017] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2014] [Revised: 02/09/2015] [Accepted: 02/10/2015] [Indexed: 12/20/2022]
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Sun W, Su L, Sheng Y, Shen Y, Chen G. Is there association between Glutathione S Transferases polymorphisms and cataract risk: a meta-analysis? BMC Ophthalmol 2015. [PMID: 26208492 PMCID: PMC4514966 DOI: 10.1186/s12886-015-0065-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Background Glutathione S transferase (GST) polymorphisms have been considered as risk factors for age-related cataracts, but the results remain controversial. In this study, we have performed a meta-analysis to evaluate the association between polymorphisms of GSTM1 and GSTT1 and cataract risk. Methods Published literature from PubMed and other databases were retrieved. The case–control studies regarding the association between GSTM1 or GSTT1 polymorphism and cataract risk were included. Pooled odds ratio (OR) and 95 % confidence interval (CI) were calculated using random- or fixed-effects model. Results Fifteen studies on GSTM1 (3,065 patients and 2,105 controls), and nine studies on GSTT1 (2,374 patients and 1,544 controls) were included. By pooling all the studies, GSTM1 null polymorphism was not associated with cataract risk, and this negative association maintained in subgroup analyses. However, GSTT1 null polymorphism was significantly associated with increased risk of posterior subcapsular (OR, 1.42; 95 % CI, 1.04–1.94) but not other subtypes of cataract. Stratified analyses demonstrated an association of GSTT1 null genotype with increased risk of cataract in Asian (OR, 1.44; 95 % CI, 1.14–1.83) but not Caucasian populations. In addition, seven pooled studies showed no association of cataract risk with the combined GSTM1 and GSTT1 null genotypes. Conclusions This meta-analysis suggests that GSTT1 null polymorphism is associated with increased risk of posterior subcapsular cataract. Given the limited sample size, the association between GSTT1 null polymorphism and cataract risk in Asian awaits further investigation.
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Affiliation(s)
- Wen Sun
- Department of Ophthalmology, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.
| | - Liling Su
- Department of Public Health, Zhejiang University School of Medicine, 866 Yuhangtang Road, 310058, Hangzhou, China.
| | - Yan Sheng
- Department of Ophthalmology, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.
| | - Ye Shen
- Department of Ophthalmology, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.
| | - Guangdi Chen
- Department of Public Health, Zhejiang University School of Medicine, 866 Yuhangtang Road, 310058, Hangzhou, China.
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Abstract
Lens opacities or cataract(s) represent a universally important cause of visual impairment and blindness. Typically, cataract is acquired with aging as a complex disorder involving environmental and genetic risk factors. Cataract may also be inherited with an early onset either in association with other ocular and/or systemic abnormalities or as an isolated lens phenotype. Here we briefly review recent advances in gene discovery for inherited and age-related forms of cataract that are providing new insights into lens development and aging.
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An Updated Meta-Analysis: Risk Conferred by Glutathione S-Transferases (GSTM1 and GSTT1) Polymorphisms to Age-Related Cataract. J Ophthalmol 2015; 2015:103950. [PMID: 25692031 PMCID: PMC4322823 DOI: 10.1155/2015/103950] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2014] [Accepted: 11/21/2014] [Indexed: 01/13/2023] Open
Abstract
Purpose. To study the effects of glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms on age-related cataract (ARC). Methods. After a systematic literature search, all relevant studies evaluating the association between GSTs polymorphisms and ARC were included. Results. Fifteen studies on GSTM1 and nine studies on GSTT1 were included in this meta-analysis. In the pooled analysis, a significant association between null genotype of GSTT1 and ARC was found (OR = 1.229, 95% CI = 1.057–1.429, and P = 0.007). In subgroup analysis, the association between cortical cataract (CC) and GSTM1 null genotype was statistically significant (OR = 0.713, 95% CI = 0.598–0.850, and P < 0.001). In addition, GSTM1 null genotype was significantly associated with ARC causing risk to individuals working indoors and not individuals working outdoors. The association between GSTT1 null genotype and risk of ARC was statistically significant in Asians (OR = 1.442, 95% CI = 1.137–1.830, and P = 0.003) but not in Caucasians. Conclusions. GSTM1 positive genotype is associated with increased risk of CC and loses the protective role in persons who work outdoors. Considering the ethnic variation, GSTT1 null genotype is found to be associated with increased risk of ARC in Asians but not in Caucasians.
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Association of vitamin A and β-carotene with risk for age-related cataract: A meta-analysis. Nutrition 2014; 30:1113-21. [DOI: 10.1016/j.nut.2014.02.025] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2013] [Revised: 02/17/2014] [Accepted: 02/25/2014] [Indexed: 11/20/2022]
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Zheng LR, Ma JJ, Zhou DX, An LF, Zhang YQ. Association between DNA repair genes (XPD and XRCC1) polymorphisms and susceptibility to age-related cataract (ARC): a meta-analysis. Graefes Arch Clin Exp Ophthalmol 2014; 252:1259-66. [PMID: 24906341 DOI: 10.1007/s00417-014-2679-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2013] [Revised: 05/17/2014] [Accepted: 05/20/2014] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND DNA repair gene (XPD and XRCC1) polymorphisms have been considered as risk factors for the development of age-related cataract (ARC). To confirm the association between DNA repair gene (XPD and XRCC1) polymorphisms and the risk of ARC, a meta-analysis was conducted. METHODS A search was made of published literature from Institute for Scientific Information (ISI) Web of Knowledge, PubMed, Google Scholar, China National Knowledge Infrastructure (CNKI), and Wanfang Data. In addition, all studies evaluating the association between DNA repair genes (XPD and XRCC1) polymorphisms and the risk for ARC were included in our analysis. Pooled odds ratio (OR) and 95 % confidence interval (CI) were calculated by using fixed- or random-effects model. The Egger's test was used to check the publication bias. RESULTS Six studies on XRCC1 Arg399Gln (1,300 cases, 1,222 controls) and five studies on XPD Lys751Gln (1,092 cases, 1,061 controls) were included. For the XPD Lys751Gln (A/C) SNP, the overall analysis demonstrated that the CC genotype showed a significant association with a decreased risk for ARC compared with the AA genotype (OR = 0.59, 95 % CI, 0.38-0.92, P = 0.019). Similarly, the CC genotype showed a significant association with a decreased risk for ARC compared with the (AA + AC) genotype (OR = 0.65, 95 % CI, 0.43-0.98, P = 0.040). Subgroup analysis showed that the association between the CC genotype and decreased risk for ARC is statistically significant in Caucasians (OR = 0.41, 95 % CI, 0.24-0.73, P = 0.002) but not in Asians (OR = 1.06, 95 % CI, 0.51-2.19, P = 0.877). For the XRCC1 Arg399Gln (G/A) SNP, the overall analysis demonstrated that the A allele showed a significant association with an increased risk for ARC compared with the G allele (OR = 1.16, 95 % CI, 1.03-1.31, P = 0.015). Subgroup analyses exhibited that the association between the A allele and the risk for ARC was statistically significant in Asians (OR = 1.23, 95 % CI, 1.07-1.41, P = 0.003) but not in Caucasians (OR = 0.94, 95 % CI, 0.73-1.22, P = 0.660). Compared with the GG genotype, the GA genotype showed a significant association with an increased risk for ARC in Asians (OR = 1.32, 95 % CI, 1.08-1.61, P = 0.006) but not in Caucasians (OR = 0.58, 95 % CI, 0.27-1.26, P = 0.171). The Egger's test did not reveal an obvious publication bias among the included studies. CONCLUSIONS Our meta-analysis suggested that the CC genotype of XPD Lys751Gln (A/C) SNP seemed to portend a decreased risk for ARC in Caucasian populations but not in Asian populations. The A allele and GA genotype of XRCC1 Arg399Gln (G/A) SNP might increase risk for ARC in Asian populations but not in Caucasian populations. More researches with larger and more different ethnic populations on this issue are therefore necessary.
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Affiliation(s)
- Lie-rui Zheng
- Medical College, Northwest University for Nationalities, Lanzhou, 730030, China,
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Chandra A, Raza ST, Abbas S, Singh L, Rizvi S, Ahmed F, Eba A, Mahdi F. Polymorphism of GST and FTO Genes in Risk Prediction of Cataract among a North Indian Population. Ophthalmic Genet 2014; 37:19-24. [PMID: 24754249 DOI: 10.3109/13816810.2014.907921] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND The present study was carried out to investigate the association of GST and FTO gene polymorphisms with cataract cases and controls. MATERIALS AND METHODS The study included 131 cases and 126 controls. GST and FTO gene polymorphisms were evaluated by PCR-RFLP. RESULTS The frequency of the GSTM1-positive and GSTT1-positive in cataract cases were 62.13% and 86.40% while in the controls it was 46.39% and 95.87% with odds ratios of 1.9 (95% CI, 1.08-3.32; p value 0.025) and 0.27 (95% CI, 0.09-0.86; p value, 0.019) respectively. There was a statistically significant association between the GSTM1 null genotype and the risk of cataract development with an odds ratio of 0.43 (95% CI, 0.24-0.76; p value, 0.003). Significant differences were obtained in the frequencies of FTO AA and TT genotype (p = 0.023 and 0.023) between cases and controls. CONCLUSION The present study suggested that GSTM1, GSTT1 and FTO gene polymorphisms are associated with increased risk for cataract in North Indian populations. Due to the limited sample size, the finding on GST and FTO gene polymorphisms need further investigation.
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Affiliation(s)
| | | | | | - Luxmi Singh
- b Opthalmology, Era's Lucknow Medical College and Hospital , Lucknow , India
| | | | | | - Ale Eba
- a Departments of Biochemistry and
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Jiang S, Hu N, Zhou J, Zhang J, Gao R, Hu J, Guan H. Polymorphisms of the WRN gene and DNA damage of peripheral lymphocytes in age-related cataract in a Han Chinese population. AGE (DORDRECHT, NETHERLANDS) 2013; 35:2435-2444. [PMID: 23334603 PMCID: PMC3824989 DOI: 10.1007/s11357-013-9512-4] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/07/2012] [Accepted: 01/09/2013] [Indexed: 06/01/2023]
Abstract
Werner syndrome is caused by mutations in the DNA repair Werner helicase (WRN) gene and characterized by accelerated aging including cataracts. Age-related cataract (ARC) cases (N = 504) and controls (N = 244) were recruited from a population-based study to evaluate the association of single-nucleotide polymorphisms (SNPs) of WRN and another DNA repair gene (human 8-oxoguanine DNA N-glycosylase 1) with ARC. Among the five SNPs tested, only WRN rs1346044 was found to be significantly associated between cases and controls before multiple-testing adjustment. The minor C allele of rs1346044 was associated with ARC with an odds ratio (OR) of 0.66, suggesting a protective role of the C allele for developing ARC. The stratification analysis on the subtypes of ARC showed that rs1346044 was significantly associated with cortical cataract, but not with nuclear, posterior subcapsular, and mixed types after multiple-testing adjustment (OR = 0.51, p< 0.01). The genetic model analysis showed that the results fit the dominant model (OR = 0.44, p < 0.001). The comet assay used to assess the extent of DNA damage in peripheral lymphocytes of ARC cases found that the DNA damage in lymphocytes from patients with CC genotype was significantly less than that in patients with TT genotype. We concluded that the C allele of rs1346044, a non-synonymous SNP resulting in the conversion of Cys to Arg at amino acid position 1367 of WRN, alters susceptibility to ARC, especially the cortical type of the disease, in the Han Chinese. The underlying mechanism of its protective role might be related to the improved DNA repair function.
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Affiliation(s)
- Shengqun Jiang
- Department of Ophthalmology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu China
| | - Nan Hu
- Department of Ophthalmology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu China
| | - Jing Zhou
- Department of Ophthalmology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu China
| | - Junfang Zhang
- Department of Ophthalmology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu China
| | - Ruifang Gao
- Department of Ophthalmology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu China
| | - Jianyan Hu
- Department of Ophthalmology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu China
| | - Huaijin Guan
- Department of Ophthalmology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu China
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Stamenkovic M, Radic T, Stefanovic I, Coric V, Sencanic I, Pljesa-Ercegovac M, Matic M, Jaksic V, Simic T, Savic-Radojevic A. Glutathione S-transferase omega-2 polymorphismAsn142Aspmodifies the risk of age-related cataract in smokers and subjects exposed to ultraviolet irradiation. Clin Exp Ophthalmol 2013; 42:277-83. [DOI: 10.1111/ceo.12180] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2013] [Accepted: 07/15/2013] [Indexed: 01/24/2023]
Affiliation(s)
- Miroslav Stamenkovic
- Medical Center Zvezdara; University Eye Clinic; Belgrade Serbia
- Faculty of Special Education and Rehabiltation; University of Belgrade; Belgrade Serbia
| | - Tanja Radic
- Faculty of Medicine; Institute of Medical and Clinical Biochemistry; University of Belgrade; Belgrade Serbia
| | - Ivan Stefanovic
- Eye Clinic; Clinical Center Serbia; Faculty of Medicine; University of Belgrade; Belgrade Serbia
| | - Vesna Coric
- Faculty of Medicine; Institute of Medical and Clinical Biochemistry; University of Belgrade; Belgrade Serbia
| | - Ivan Sencanic
- Medical Center Zvezdara; University Eye Clinic; Belgrade Serbia
| | - Marija Pljesa-Ercegovac
- Faculty of Medicine; Institute of Medical and Clinical Biochemistry; University of Belgrade; Belgrade Serbia
| | - Marija Matic
- Faculty of Medicine; Institute of Medical and Clinical Biochemistry; University of Belgrade; Belgrade Serbia
| | - Vesna Jaksic
- Medical Center Zvezdara; University Eye Clinic; Belgrade Serbia
| | - Tatjana Simic
- Faculty of Medicine; Institute of Medical and Clinical Biochemistry; University of Belgrade; Belgrade Serbia
| | - Ana Savic-Radojevic
- Faculty of Medicine; Institute of Medical and Clinical Biochemistry; University of Belgrade; Belgrade Serbia
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Chi C, Tian R, Liu H, Wang H, Wei J, Guo J, Guo F, Li S. Follow-up study of abnormal biological indicators and gene expression in the peripheral blood of three accidentally exposed persons. JOURNAL OF RADIATION RESEARCH 2013; 54:840-51. [PMID: 23559597 PMCID: PMC3766294 DOI: 10.1093/jrr/rrt022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/12/2012] [Revised: 01/16/2013] [Accepted: 02/27/2013] [Indexed: 05/19/2023]
Abstract
In order to identify biomarkers for early diagnosis and/or for therapeutic targets in the delayed health effects of ionizing radiation, we analyzed the subgroups of lymphocytes, serum protein levels and gene expression profiles in the peripheral blood of three ⁶⁰Co γ-ray accidentally exposed persons during the three years after irradiation. Flow cytometry analyses and agarose gel electrophoresis were applied to investigate the subgroups of lymphocytes and the composition of serum proteins, respectively. Gene expression profiling was obtained using a whole genome gene expression chip assay. Both the percentage of CD4+ T lymphocytes and the ratio of Th to Ts were reduced compared with the normal control values. The percentage of albumin decreased whereas beta globulin increased. There were 285 up-regulated and 446 down-regulated genes in irradiated samples relative to the control samples. The expression of KDR, CEACAM8 and OSM was validated by RT-PCR. The majority of the differentially expressed genes encode proteins associated with the immune response, inflammation, oncogenesis, cell structure, oxidative stress, neuro-hormone regulation, reproduction, susceptibility to psychiatric disorders, or transcriptional regulation. We have identified a number of promising novel candidates that have potential for serving as biomarkers for delayed damage. Furthermore, the changes in the immunological indicator CD4+ T cells, and the ratio of CD4+ T to CD8+ T cells may be biomarkers for the prediction of delayed damage by ionizing radiation. The findings of our study are useful for forming a comprehensive understanding of the mechanisms underlying the delayed effects of ionizing radiation.
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Affiliation(s)
- Cuiping Chi
- Department of Radiation Medicine and Environmental Medicine, China Institute for Radiation Protection, Taiyuan, 030006, China
- Corresponding author. Tel: +86-351-220-2218; Fax: +86-351-702-0407;
| | - Rong Tian
- Affiliated Hospital of China Institute for Radiation Protection
| | - Huifang Liu
- Shanxi Center for Disease Control and Prevention, Xiao Nan Guan Street No.8, Taiyuan, 030012, China
| | - Haiyan Wang
- Department of Radiation Medicine and Environmental Medicine, China Institute for Radiation Protection, Taiyuan, 030006, China
| | - Jinping Wei
- Department of Radiation Medicine and Environmental Medicine, China Institute for Radiation Protection, Taiyuan, 030006, China
| | - Jianping Guo
- Department of Radiation Medicine and Environmental Medicine, China Institute for Radiation Protection, Taiyuan, 030006, China
| | - Fengling Guo
- Affiliated Hospital of China Institute for Radiation Protection
| | - Shufang Li
- Department of Radiation Medicine and Environmental Medicine, China Institute for Radiation Protection, Taiyuan, 030006, China
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Shiels A, Hejtmancik JF. Genetics of human cataract. Clin Genet 2013; 84:120-7. [PMID: 23647473 PMCID: PMC3991604 DOI: 10.1111/cge.12182] [Citation(s) in RCA: 107] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2013] [Revised: 04/30/2013] [Accepted: 04/30/2013] [Indexed: 12/15/2022]
Abstract
The pathogenesis of inherited cataracts of all kinds recapitulates the developmental and cell biology of the lens. Just as each novel mutation provides additional information about the structural or functional biology of the affected gene, each newly identified gene provides insight into the developmental and cellular biology of the lens. The set of genes currently known to be associated with cataract is far from complete, especially for age-related cataract, and there is much additional information to be discovered through further genetic studies.
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Affiliation(s)
- A Shiels
- Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA
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Are glutathione S-transferase polymorphisms (GSTM1, GSTT1) associated with primary open angle glaucoma? A meta-analysis. Gene 2013; 527:311-5. [PMID: 23827458 DOI: 10.1016/j.gene.2013.06.031] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2013] [Revised: 06/05/2013] [Accepted: 06/10/2013] [Indexed: 11/21/2022]
Abstract
BACKGROUND Glutathione S-transferase (GST) variants have been considered as risk factors for the pathogenesis of primary open angle glaucoma (POAG). However, the results have been inconsistent. In this study, we performed a meta-analysis to assess the association between GSTM1 and GSTT1 null genotypes and the risk for POAG. METHODS Published literature from PubMed and EMBASE databases was retrieved. All studies evaluating the association between GSTM1/GSTT1 variants and POAG were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed- or random-effects model. RESULTS 14 studies (1711 POAG cases and 1537 controls) were included in the meta-analysis of GSTM1 genotypes and 10 studies (1306 POAG cases and 1114 controls) were included in the meta-analysis of GSTT1 genotypes. The overall result showed that the association between GSTM1 and GSTT1 null genotypes and risk for POAG was not statistically significant (GSTM1: OR=1.19, 95% CI=0.82-1.73, p=0.361; GSTT1: OR=1.26, 95% CI=0.77-2.06, p=0.365). The results by ethnicity showed that the association between the GSTM1 null genotype and risk for POAG is statistically significant in East Asians (OR=1.41, 95% CI=1.04-1.90, p=0.026), but not in Caucasians (OR=1.13, 95% CI=0.69-1.84, p=0.638) and Latin-American (OR=1.09, 95% CI=0.62-1.92, p=0.767). In addition, there was no significant association of GSTT1 null genotype with risk for POAG in either ethnic population. CONCLUSIONS The present meta-analysis suggested that there might be a significant association of GSTM1 null genotype with POAG risk in East Asians.
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Huang W, Wang W, Zhou M, Chen S, Zhang X. Association of glutathione S-transferase polymorphisms (GSTM1 and GSTT1) with primary open-angle glaucoma: an evidence-based meta-analysis. Gene 2013; 526:80-6. [PMID: 23747403 DOI: 10.1016/j.gene.2013.05.032] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2013] [Revised: 04/27/2013] [Accepted: 05/15/2013] [Indexed: 01/11/2023]
Abstract
Studies investigating the associations between glutathione S-transferase (GST) genetic polymorphisms and primary open-angle glaucoma (POAG) have reported controversial results. Therefore, a meta-analysis was performed to clarify the effects of GSTM1 and GSTT1 polymorphisms on POAG risk. Published literatures from PubMed, EMBASE, ISI Web of Science and CBM databases were retrieved. All studies evaluating the association between GSTM1/GSTT1 polymorphisms and POAG were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed- or random-effects model. Eleven studies on GSTM1 (1339 cases and 1412 controls) and seven studies on GSTT1 (958 cases, 1003 controls) were included. Overall analysis showed that the association between GSTM1 and GSTT1 null genotype and POAG risk is not statistically significant. Subgroup analyses showed that the null genotype of GSTM1 increased the risk of POAG in Asians. In GSTM1-GSTT1 interaction analysis, individuals with dual null genotype were associated with a significantly increased risk of POAG when compared with the dual present genotype. In conclusion, the present meta-analysis suggested that GSTM1 null genotypes are associated with increased POAG risk in Asian populations but not in Caucasian and mixed populations. Dual null genotype of GSTM1/GSTT1 is associated with increased risk of POAG. Given the limited sample size, the finding on GST polymorphisms needs further investigation.
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Affiliation(s)
- Wenbin Huang
- Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-sen University, Guangzhou, People's Republic of China
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Yu Y, Weng Y, Guo J, Chen G, Yao K. Association of glutathione S transferases polymorphisms with glaucoma: a meta-analysis. PLoS One 2013; 8:e54037. [PMID: 23342067 PMCID: PMC3544666 DOI: 10.1371/journal.pone.0054037] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2012] [Accepted: 12/07/2012] [Indexed: 11/19/2022] Open
Abstract
Background Glutathione S transferase (GST) polymorphisms have been considered risk factors for the development of glaucoma, including primary open angle glaucoma (POAG) and other types of glaucoma. However, the results remain controversial. In this study, we have conducted a meta-analysis to assess the association between polymorphisms of GSTM1, GSTT1 and GSTP1 and glaucoma risk. Methods Published literature from PubMed and other databases were retrieved. All studies evaluating the association between GSTM1, GSTT1 and GSTP1 polymorphisms and glaucoma risk were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random- or fixed-effects model. Results Twelve studies on GSTM1 (1109 cases and 844 controls), ten studies on GSTT1 (709 cases and 664 controls) and four studies on GSTP1 (543 cases and 511 controls) were included. By pooling all the studies, either GSTM1 or GSTT1 null polymorphism was not associated with a POAG risk, and this negative association maintained in Caucasian. The GSTP1 Ile 105 Val polymorphism was significantly correlated with increased POAG risk among Caucasian in a recessive model (Val/Val vs. Ile/Ile+Ile/Val: OR, 1.62, 95%CI: 1.00–2.61). Interestingly, increased glaucoma risk was associated with the combined GSTM1 and GSTT1 null genotypes (OR, 2.20; 95% CI, 1.47–3.31), and with the combined GSTM1 null and GSTP1 Val genotypes (OR, 1.86; 95% CI, 1.15–3.01). Conclusions This meta-analysis suggests that combinations of GST polymorphisms are associated with glaucoma risk. Given the limited sample size, the associations between single GST polymorphism and glaucoma risk await further investigation.
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Affiliation(s)
- Yibo Yu
- Eye Center of the 2 Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yu Weng
- Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jing Guo
- Department of Public Health, Zhejiang University School of Medicine, Hangzhou, China
| | - Guangdi Chen
- Department of Public Health, Zhejiang University School of Medicine, Hangzhou, China
- * E-mail: (GC); (KY)
| | - Ke Yao
- Eye Center of the 2 Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- * E-mail: (GC); (KY)
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The Impact of Senile Cataract Maturity on Blood Oxidative Stress Markers and Glutathione-Dependent Antioxidants: Relations with Lens Variables. J Med Biochem 2012. [DOI: 10.2478/v10011-012-0003-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
The Impact of Senile Cataract Maturity on Blood Oxidative Stress Markers and Glutathione-Dependent Antioxidants: Relations with Lens VariablesOxidative stress is implicated in senile cataract (SC) genesis, although the impact of SC maturity on blood oxidative stress markers is unclear. Total hydroperoxides, malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) were measured in the blood and lens samples of patients having either immature (n=31) or mature SC (n=50), and in 22 blood samples from noncataract controls. Compared to controls, SC patients had higher plasma MDA and serum GST, and decreased plasma GR and GSH levels. Plasma GPx as well as hydroperoxides differed from control values only in patients with mature SC. The multivariate logistic regression analysis showed that the fall of plasma GR activity (OR 5.14; CI 1.82-14.51;p=0.0020), as well as serum GST activity (OR 3.84; CI 1.36-10.83;p=0.0108) were independently associated with the maturity of SC. Lens hydroperoxides, MDA and GST, showed no correlation with correspondent blood values, in contrast to GPx (r=0.715; p<0.001) and GR (r=0.703; p<0.001). This study showed that the severity of SC is associated with increased systemic oxidative stress, which could be due to the fall of GSH-dependent antioxidant enzymes activities.
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Saify K, Saadat I, Saadat M. Genetic polymorphisms of glutathione S-transferase T1 (GSTT1) and M1 (GSTM1) in selected populations of Afghanistan. Mol Biol Rep 2012; 39:7855-9. [PMID: 22539183 DOI: 10.1007/s11033-012-1628-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2011] [Accepted: 04/16/2012] [Indexed: 01/18/2023]
Abstract
Genetic polymorphisms in genes encoding glutathione S-transferase T1 (GSTT1, a member of class theta) and M1 (GSTM1, a member of class mu) have been defined. Previous studies have revealed that there was significant difference between populations for allelic frequency of several members of GSTs. In order to find the prevalence of null genotypes of GSTM1 and GSTT1 in Afghanis populations the present study was carried out. The total study subjects consisted of 656 unrelated healthy Afghanis refugees living in Fars province (southern Iran). From these 257, 217, 120, and 62 individuals were Pashtuns, Tajiks, Hazaras, and Uzbeks, respectively. Genetic polymorphisms for GSTT1 and GSTM1 were detected by multiplex PCR. The prevalence of null genotype of GSTM1 in Pashtuns, Tajiks, Hazaras, and Uzbeks was 42.4, 48.4, 52.5, and 40.3 %, respectively. There was no significant difference between these populations for the genotypic distribution of the GSTM1 polymorphism (χ(2) = 4.67, df = 3, P = 0.197). The frequency of GSTT1 null genotype in Pashtuns, Tajiks, Hazaras, and Uzbeks was 7.4, 25.3, 25.0, and 29.0 %, respectively. The observed difference between populations for prevalence of GSTT1 null genotype was statistically significant (χ(2) = 35.54, df = 3, P < 0.001). In comparison with European and Asian populations, Afghanistan populations like Iranian populations showed intermediate frequency for GSTT1 and GSTM1 null genotypes.
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Affiliation(s)
- Khyber Saify
- Department of Biology, College of Sciences, Shiraz University, 71454 Shiraz, Iran
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Total activity of glutathione-S-transferase (GST) and polymorphisms of GSTM1 and GSTT1 genes conferring risk for the development of age related cataracts. Exp Eye Res 2012; 98:67-74. [PMID: 22446016 DOI: 10.1016/j.exer.2012.03.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2011] [Revised: 02/29/2012] [Accepted: 03/05/2012] [Indexed: 11/23/2022]
Abstract
The pathogenesis of cataract is influenced by a number of factors including oxidative stress. Glutathione-S-transferase (GST) catalyses the nucleophilic addition of the thiol of GSH to electrophilic acceptors. It is important for detoxification of xenobiotics in order to protect tissues from oxidative damage. In humans, GSTT1 and GSTM1 deletion genotypes are associated with a variety of pathological conditions including certain ophthalmic diseases. In the present study, it is aimed to determine the risk of genetic polymorphisms of GSTM1 and GSTT1 isoforms of GST for developing of age related cataracts (ARCs). We compared the prevalence of GSTT1 and GSTM1 deletion genotypes, which were determined by multiplex polymerase chain reaction, in 455 patients with ARCs (108 with nuclear (NC), 105 with cortical (CC), 96 with posterior subcapsular, (PSC) and 146 with mixed type (MT)) and 205 age and sex matched controls. The GST activity in erythrocytes (RBC) and cataractous lenses was measured spectrophotometrically using 1-chloro-2,4-dinitrobenzene (CDNB) as substrate. The frequency of GSTM1 positive individuals was significantly higher in MT cataracts followed by NC, CC and PSC types with corresponding decrease in the GSTM1 null genotypes as compared to controls. Considering the GSTT1 locus, GSTT1 null genotypes showed high frequency in patients in general as compared to controls with corresponding reduction in the GSTT1 positive genotype. The activity of GST in RBC was higher in all the types of cataracts as compared to that in controls and in cataractous lenses the mean values were slightly higher in cases of NC cataracts as compared to CC, PSC and MT. The data suggests that GSTM1 positive, GSTT1 null and double null (GSTM1 null and GSTT1 null) genotypes may confer risk for the development of ARC. The increased activity of GST found in the present study could be due to a compensatory mechanism operating in response to increased oxidative stress.
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Li Y, Xi B, Li K, Wang C. Association between vitamin D receptor gene polymorphisms and bone mineral density in Chinese women. Mol Biol Rep 2011; 39:5709-17. [PMID: 22193625 DOI: 10.1007/s11033-011-1380-3] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2011] [Accepted: 12/13/2011] [Indexed: 02/06/2023]
Abstract
Vitamin D receptor (VDR) is implicated in the regulation of bone mineral density (BMD). In this study, we performed a meta-analysis to evaluate the association between the VDR BsmI (rs1544410) and ApaI (rs7975232) polymorphisms and BMD in Chinese women. Literature was retrieved from PubMed and other databases. The studies on the association between VDR BsmI and ApaI genotypes and BMD at the lumbar spine, the femoral neck, the trochanter or the Ward's triangle in Han Chinese women were included in this meta-analysis. Pooled BMD differences and 95% confidence intervals (CIs) were calculated using random- or fixed- effects model. Twenty-five eligible studies, which included 4,075 Chinese women, were identified. No significant difference was observed for either genotype when the meta-analysis was limited to premenopausal women. In postmenopausal women, BMD differences were significant for BB vs. Bb [-0.029 (95% CI -0.056, -0.002) g/m(2), P = 0.037] at the femoral neck, AA vs. Aa [-0.029 (95% CI -0.051, -0.006) g/m(2), P = 0.012] at the lumbar spine, and Aa vs. aa [0.022(95% CI 0.011, 0.033) g/m(2), P = 0.000] at the trochanter. These results suggest a modest but statistically significant association between VDR BsmI and ApaI polymorphisms and BMD in Chinese postmenopausal women, with higher BMD in heterozygous subjects. More epidemiological and mechanistic studies are needed to further investigate the role of VDR gene polymorphisms in regulating BMD and osteoporosis in the future.
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Affiliation(s)
- Yufei Li
- Department of Orthopaedics, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, China.
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Xi B, Chen J, Yang L, Wang W, Fu M, Wang C. GABBR1 gene polymorphism(G1465A)isassociated with temporal lobe epilepsy. Epilepsy Res 2011; 96:58-63. [PMID: 21621395 DOI: 10.1016/j.eplepsyres.2011.04.014] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2011] [Revised: 04/11/2011] [Accepted: 04/29/2011] [Indexed: 11/20/2022]
Abstract
PURPOSE γ-Aminobutyric acid B receptor 1(GABBR1) gene G1465A polymorphism has been considered as a potential risk factor for the development of temporal lobe epilepsy (TLE). However, the results were inconsistent. In this study, we performed a meta-analysis to assess the association between GABBR1 G1465A polymorphism and the risk of TLE. METHODS Biomedical literature databases including PubMed, ISI web of science and Embase were searched. The studies evaluating the association between GABBR1 G1465A polymorphism and TLE were included. Pooled odds ratio (OR) and 95%CI confidence interval (CI) were calculated using fixed- or random-effects model. KEY FINDINGS Seven studies (1011 cases and 2184 controls) met the inclusion criteria and were included in the meta-analysis. The overall result showed that the association between GABBR1 G1465A polymorphism was statistically significant (OR=5.381, 95%CI: 1.726, 16.776, P=0.004). Subgroup analysis showed that the effect estimate was higher in the studies with high quality score (OR=14.220, 95%CI: 6.933, 29.169, P=0.000) than that in the studies with low quality score (OR=1.158, 95%CI: 0.325, 4.123, P=0.821). SIGNIFICANCE The present meta-analysis suggests that GABBR1 G1465A polymorphism is associated with the risk of TLE. The role of GABBR1 G1465A polymorphism in the development of TLE merits further investigation.
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Affiliation(s)
- Bo Xi
- Department of Maternal and Child Health Care, School of Public Health, Shandong University, Jinan 250012, China
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Zhang S, Wang C, Xi B, Li X. Association between the tumour necrosis factor-α-308G/A polymorphism and chronic obstructive pulmonary disease: an update. Respirology 2011; 16:107-15. [PMID: 20946339 DOI: 10.1111/j.1440-1843.2010.01879.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND AND OBJECTIVE Previous studies have suggested that the -308A allele in the tumour necrosis factor-α (TNF-α) gene promoter (rs1800629) may be a potential risk factor for COPD. However, more recent findings have been inconsistent. In the present study, a meta-analysis was performed to assess the association between the TNF-α-308G/A single nucleotide polymorphism (SNP) and the risk of COPD. METHODS Published studies were retrieved from PubMed, EMBASE and other databases. All studies assessing the association between the TNF-α-308G/A SNP and the risk of COPD were assessed. Pooled ORs with 95% CIs were calculated. RESULTS In the 36 studies that met the inclusion criteria, 4975 patients and 6518 control subjects had been genotyped. The overall results showed that the association between the TNF-α-308G/A SNP and the risk of COPD was statistically significant for Asians (OR = 2.36, 95% CI: 1.84-3.02, P < 0.0001) but not for Caucasians (OR = 1.07, 95% CI: 0.91-1.25, P = 0.438). As smoking is one of the most important risk factors for COPD, a second meta-analysis that included only smokers (3018 patients and 2749 control subjects) was performed. This analysis confirmed that the association between the TNF-α-308G/A SNP and COPD was statistically significant for Asians (OR = 1.72, 95% CI: 1.14-2.61, P = 0.011) but not for Caucasians (OR = 1.16, 95% CI: 0.86-1.56, P = 0.33). CONCLUSIONS This meta-analysis suggests that the TNF-α-308A genotype is associated with an increased risk of COPD in Asian but not Caucasian populations. Further studies are necessary to evaluate the relationship between TNF-α polymorphisms and the risk of COPD.
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Affiliation(s)
- Shihua Zhang
- College of Bioinformatics Science and Technology, Harbin Medical University, China
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Association of the CYP3A5 polymorphism (6986G>A) with blood pressure and hypertension. Hypertens Res 2011; 34:1216-20. [PMID: 21814220 DOI: 10.1038/hr.2011.112] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
The cytochrome P450 family 3 subfamily A polypeptide 5 (CYP3A5) gene has been implicated in the regulation of blood pressure (BP) and thus, may serve as a potential risk factor for the development of hypertension. However, current results regarding the association between CYP3A5 single nucleotide polymorphisms and BP/hypertension have been inconsistent. In this study, we performed a meta-analysis to evaluate the association between the CYP3A5 rs776746 (6986G>A) polymorphism and BP/hypertension. Ten studies (representing 2799 cases and 6794 controls) were included to determine the association of this single nucleotide polymorphism with hypertension, and 12 studies (9076 subjects) were included to determine the association of this single nucleotide polymorphism with BP. Overall, no associations were observed between the rs776746 polymorphism and BP/hypertension. In subgroup analysis, CYP3A5*1 carriers had lower systolic BP, compared with non-carriers in white populations (mean difference=-1.322, 95% confidence interval -2.401 to -0.242 mm Hg, P=0.016). This meta-analysis suggested a modestly significant association between the CYP3A5 rs776746 polymorphism and systolic BP in white populations. Given the limited sample size, additional studies are necessary to investigate the role of CYP3A5 in the regulation of BP and the pathogenesis of hypertension.
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Yu L, Wang CY, Xi B, Sun L, Wang RQ, Yan YK, Zhu LY. GST polymorphisms are associated with hepatocellular carcinoma risk in Chinese population. World J Gastroenterol 2011; 17:3248-56. [PMID: 21912475 PMCID: PMC3158402 DOI: 10.3748/wjg.v17.i27.3248] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2010] [Revised: 12/11/2010] [Accepted: 12/18/2010] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the association between GSTM1 and GSTT1 polymorphisms and the risk of hepatocellular carcinoma (HCC) in Chinese population.
METHODS: Literature databases including PubMed, ISI web of science and other databases were searched. Pooled odds ratio (OR) and 95% CI were calculated using random- or fixed- effects model. Subgroup analysis and sensitivity analysis were also performed.
RESULTS: Nineteen studies of GSTM1 (2660 cases and 4017 controls) and 16 studies of GSTT1 (2410 cases and 3669 controls) were included. The GSTM1/GSTT1 null genotypes were associated with increased risk of HCC in Chinese population (for GSTM1, OR = 1.487, 95% CI: 1.159 to 1.908, P = 0.002; for GSTT1, OR = 1.510, 95% CI: 1.236 to 1.845, P = 0.000). No publication bias was detected. In subgroup analysis, glutathione S-transferases polymorphisms were significantly associated with HCC risk among the subjects living in high-incidence areas, but not among the subjects living in low-incidence areas.
CONCLUSION: The present meta-analysis suggests that GSTM1/GSTT1 null genotypes are associated with increased risk of HCC in Chinese population.
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Xi B, Zeng T, Liu W. Catechol-O-methyltransferase Val158Met polymorphism in breast cancer risk. Breast Cancer Res Treat 2011; 126:839-40; author reply 841. [PMID: 21221767 DOI: 10.1007/s10549-010-1337-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2010] [Accepted: 12/22/2010] [Indexed: 01/25/2023]
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