Association between polymorphisms of OGG1, EPHA2 and age-related cataract risk: a meta-analysis.
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ABSTRACT:
SUBMITTER: Zhang H
PROVIDER: S-EPMC5041552 | biostudies-literature | 2016 Sep
REPOSITORIES: biostudies-literature
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Association between polymorphisms of OGG1, EPHA2 and age-related cataract risk: a meta-analysis.
Zhang Hongxu H Zhong Jianguang J Bian Zhenyu Z Fang Xiang X Peng You Y Hu Yongping Y
BMC ophthalmology 20160929 1
<h4>Background</h4>Evidences have identified the correlation of 8-oxoguanine DNA glycosylase-1 (OGG1) and eph-receptor tyrosine kinase-type A2 (EPHA2) polymorphisms in age-related cataract (ARC) risk. However, the results were not consistent. The objective of this study was to examine the role of these two gene polymorphisms in ARC susceptibility.<h4>Methods</h4>Eligible case-control studies published between January 2000 and 2015 were searched and retrieved in the electronic databases. The odds ...[more]
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Project description:PurposeTo discern and confirm genetic biomarkers that help identify populations at high risk for age-related cataract (ARC).MethodsA 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.ResultsA 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).ConclusionsPolymorphisms of OGG1 and MTHFR genes are associated with ARC susceptibility and may help identify populations at high risk for ARC.
| S-EPMC5333819 | biostudies-literature
Project description:ObjectiveWe investigated whether previously reported single nucleotide polymorphisms (SNPs) of EPHA2 in European studies are associated with cataract in India.MethodsWe carried out a population-based genetic association study. We enumerated randomly sampled villages in two areas of north and south India to identify people aged 40 and over. Participants attended a clinical examination including lens photography and provided a blood sample for genotyping. Lens images were graded by the Lens Opacification Classification System (LOCS III). Cataract was defined as a LOCS III grade of nuclear ≥4, cortical ≥3, posterior sub-capsular (PSC) ≥2, or dense opacities or aphakia/pseudophakia in either eye. We genotyped SNPs rs3754334, rs7543472 and rs11260867 on genomic DNA extracted from peripheral blood leukocytes using TaqMan assays in an ABI 7900 real-time PCR. We used logistic regression with robust standard errors to examine the association between cataract and the EPHA2 SNPs, adjusting for age, sex and location.Results7418 participants had data on at least one of the SNPs investigated. Genotype frequencies of controls were in Hardy-Weinberg Equilibrium (p>0.05). There was no association of rs3754334 with cataract or type of cataract. Minor allele homozygous genotypes of rs7543472 and rs11260867 compared to the major homozygote genotype were associated with cortical cataract, Odds ratio (OR) = 1.8, 95% Confidence Interval (CI) (1.1, 3.1) p = 0.03 and 2.9 (1.2, 7.1) p = 0.01 respectively, and with PSC cataract, OR = 1.5 (1.1, 2.2) p = 0.02 and 1.8 (0.9, 3.6) p = 0.07 respectively. There was no consistent association of SNPs with nuclear cataract or a combined variable of any type of cataract including operated cataract.ConclusionsOur results in the Indian population agree with previous studies of the association of EPHA2 variants with cortical cataracts. We report new findings for the association with PSC which is particularly prevalent in Indians.
| S-EPMC3297613 | biostudies-literature
Project description:PURPOSE: The gene for Eph-receptor tyrosinekinase-type A2 (EPHA2) has been shown to be involved in the pathogenesis of age-related cataract (ARC). The aim of this study was to examine whether EPHA2 polymorphisms were associated with the susceptibility to age-related cortical cataract in a Han Chinese population. METHODS: Five single-nucleotide polymorphisms (SNPs)-rs3768293, rs3754334, rs7548209, rs707455, and rs477558-in the EPHA2 gene were genotyped in 422 Han Chinese patients with age-related cortical cataract and 317 age-, sex-, and ethnically matched healthy controls using a PCR restriction fragment length polymorphism (PCR-RFLP) assay. Data were analyzed by ?(2) analysis. RESULTS: The results showed that the five analyzed polymorphisms in EPHA2 were in Hardy-Weinberg equilibrium both in the patients and in the controls. The frequency of the rs477558 AA genotype was signi?cantly increased in ARC patients compared with controls (?(2)=8.649, pc=0.045, odds ratio [OR] 1.555, 95% CI 1.158 to 2.089). The frequency of the rs477558 AG genotype was signi?cantly decreased in ARC patients compared with controls (?(2)=9.281, pc=0.030, OR 0.626, 95% CI 0.463 to 0.847). Signi?cantly higher frequencies of the GG genotype and the G allele of rs7548209 were observed in ARC patients compared with controls (?(2)=10.430, pc=0.015, OR 1.660, 95% CI 1.219 to 2.261 and ?(2)=8.537, pc=0.015, OR 1.486, 95% CI 1.138 to 1.940, respectively). On the other hand, signi?cantly decreased frequencies of the rs7548209 CG genotype and the C allele were observed in ARC patients compared with controls (?(2)=9.999, pc=0.030, OR 0.603, 95% CI 0.440 to 0.826 and ?(2)=8.537, pc=0.015, OR 0.673, 95% CI 0.515 to 0.879, respectively). There was no difference in the frequencies of the genotype and allele of the rs3768293, rs3754334, and rs707455 SNPs between the patients with ARC and the controls. CONCLUSIONS: Our study suggests that both SNP rs477558 and SNP rs7548209 of EPHA2 are associated with age-related cortical cataract in a Han Chinese population.
| S-EPMC3115745 | biostudies-literature
Project description:BackgroundRecent clinical studies have assessed the association of various polymorphisms on the ephreceptor tyrosinekinase-type A2 (EPHA2) with the risk for age-related cataract in populations of different ethnic/racial backgrounds, but inconsistent results have been obtained.ObjectiveThis meta-analysis aimed to identify if any polymorphism(s) might be commonly present in different ethnic/racial populations in association with the age-related cataract risk.MethodsThe PubMed and Web of Science databases (up to December 1, 2012) were searched for clinical studies on the association of EPHA2 polymorphisms with the risk for age-related cataract. The polymorphisms that were assessed in all eligible studies were analyzed for their association with the risk for age-related cataract using different models.ResultsThree studies were identified, which were conducted, respectively, on white Americans in the Unites States and on Asians in Indian and China. The polymorphism, rs3754334, was the only one studied in all these three studies and was therefore the focus of this meta-analysis. No publication bias or heterogeneity was found. Our analysis results demonstrated that rs3754334 was associated with the risk of any cataracts in the recessive (OR = 1.202, 95% CI: 1.051-1.375, P = 0.007) and Codominant (OR = 1.194, 95% CI: 1.035-1.378, P = 0.015) models, but its association with cortical or nuclear phenotype of age-related cataract was not evident.ConclusionPolymorphism, rs3754334, might be a variant on the EPHA2 gene that is commonly associated with the risk for age-related cataract in different ethnical and geographical populations.
| S-EPMC3745390 | biostudies-literature
Project description:PurposeTo analyze the association of the polymorphisms of xeroderma pigmentosum complementation group D (XPD) and 8-oxoguanine glycosylase-1 (OGG1) genes with the risk of age-related cataract (ARC) in an Egyptian population.MethodsThis case-control study included 150 patients with ARC and 50 controls. Genotyping of XPD Asp³¹²Asn was performed by amplification refractory mutation system PCR assay and genotyping of OGG1 Ser³²⁶Cys was carried out by PCR including confronting two-pair primers.ResultsThe Asn/Asn genotype of XPD gene was significantly associated with increased risk of ARC (odds ratio [OR] = 2.74, 95% confidence interval [CI] = 1.01-7.43, p = 0.04) and cortical cataract (OR = 5.06, 95% CI = 1.70-15.05, p = 0.002). The Asn³¹² allele was significantly associated with an increased risk of ARC (OR = 1.75, 95% CI 1.06-2.89, p = 0.03) and cortical cataract (OR = 2.81, 95% CI = 1.56-5.08, p<0.001). The OGG1 Cys/Cys genotype frequency was significantly higher in ARC (OR = 4.13, 95% CI = 0.93-18.21, p = 0.04) and the Cys(³²⁶ allele (OR = 1.85, 95% CI = 1.07-3.20, p = 0.03). Moreover, the Cys/Cys genotype of the OGG1 gene was significantly higher in cortical cataract (OR = 6.00, 95% CI = 1.24-28.99, p = 0.01) and the Cys³²⁶ allele was also significantly associated with cortical cataract (OR = 2.45, 95% CI = 1.30-4.63, p = 0.005).ConclusionsThe results suggest that the Asn/Asn genotype and Asn³¹² allele of XPD polymorphism, as well as the Cys/Cys genotype and Cys³²⁶ allele of the OGG1 polymorphism, may be associated with increased risk of the development of ARC, particularly the cortical type, in the Egyptian population.
| S-EPMC4029483 | biostudies-literature
Project description:BackgroundThe base excision repair (BER) pathway removes DNA damage caused by ionizing radiation, reactive oxidative species and methylating agents. OGG1 and APE1 are two important genes in the BER pathway. Many epidemiological studies have evaluated the association between polymorphisms in the two BER genes (OGG1 Ser326Cys and APE1 Asp148Glu) and breast cancer risk. However, the results are inconsistent.MethodsWe searched the electronic databases including PubMed, Embase and Cochrane library for all eligible studies for the period up to February 2014. Data were extracted by two independent authors and pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to assess the strength of the association.ResultsA total of 17 studies including 9,040 cases and 10,042 controls were available for OGG1 Ser326Cys polymorphism and 7 studies containing 2,979 cases and 3,111 controls were included for APE1 Asp148Glu polymorphism. With respect to OGG1 Ser326Cys polymorphism, we did not find a significant association with breast cancer risk when all eligible studies were pooled into the meta-analysis. However, in subgroup analyses by ethnicity and menopausal status, statistical significant increased breast cancer risk was found in Asian populations (Cys/Cys vs. Ser/Ser: OR=1.157, 95% CI 1.013-1.321, P=0.011; Cys/Cys vs. Ser/Cys+Ser/Ser: OR=1.113, 95% CI 1.009-1.227, P=0.014) and postmenopausal patients (Cys/Cys vs. Ser/Cys+Ser/Ser: OR=1.162, 95% CI 1.003-1.346, P=0.024). In subgroup analysis according to quality score, source of control, and HWE in controls, no any significant association was detected. With respect to APE1 Asp148Glu polymorphism, no significant association with breast cancer risk was demonstrated in the overall and stratified analyses.ConclusionsThe present meta-analysis suggests that the OGG1 Ser326Cys polymorphism may be a risk factor for breast cancer in Asians and postmenopausal patients. Further large and well-designed studies are needed to confirm this association.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1156934297124915.
| S-EPMC4064811 | biostudies-literature
Project description:Age-related cataract is a major cause of blindness worldwide, and cortical cataract is the second most prevalent type of age-related cataract. Although a significant fraction of age-related cataract is heritable, the genetic basis remains to be elucidated. We report that homozygous deletion of Epha2 in two independent strains of mice developed progressive cortical cataract. Retroillumination revealed development of cortical vacuoles at one month of age; visible cataract appeared around three months, which progressed to mature cataract by six months. EPHA2 protein expression in the lens is spatially and temporally regulated. It is low in anterior epithelial cells, upregulated as the cells enter differentiation at the equator, strongly expressed in the cortical fiber cells, but absent in the nuclei. Deletion of Epha2 caused a significant increase in the expression of HSP25 (murine homologue of human HSP27) before the onset of cataract. The overexpressed HSP25 was in an underphosphorylated form, indicating excessive cellular stress and protein misfolding. The orthologous human EPHA2 gene on chromosome 1p36 was tested in three independent worldwide Caucasian populations for allelic association with cortical cataract. Common variants in EPHA2 were found that showed significant association with cortical cataract, and rs6678616 was the most significant in meta-analyses. In addition, we sequenced exons of EPHA2 in linked families and identified a new missense mutation, Arg721Gln, in the protein kinase domain that significantly alters EPHA2 functions in cellular and biochemical assays. Thus, converging evidence from humans and mice suggests that EPHA2 is important in maintaining lens clarity with age.
| S-EPMC2712078 | biostudies-literature
Project description:To evaluate the effects of OGG1 (Ser326Cys, 11657A/G, and Arg154His) and APE1 (Asp148Glu, and T-656G) polymorphisms on colorectal cancer (CRC) risk.We enrolled 727 cases newly diagnosed with colorectal adenocarcinoma and 736 age- and sex-matched healthy controls from a medical center in Taiwan. Genomic DNA isolated from the buffy coat was used for genotyping through polymerase chain reaction. Unconditional logistic regressions were used for calculating ORs and 95%CIs to determine the association between the genetic polymorphisms and CRC risk. Haplotype frequencies were estimated using PHASE software. Moreover, stratification analyses on the basis of sex, age at diagnosis, and tumor subsite and stage were performed.The CRC risk was higher in patients with the OGG1 326Ser/Cys + Cys/Cys genotype (OR = 1.38, 95%CI: 1.03-1.85, P = 0.030), particularly high in patients with stage III + IV cancer (OR = 1.48, 95%CI: 1.03-2.13) compared with patients with the Ser/Ser genotype. In addition, OGG1 11657G allele carriers had a 41% reduced CRC risk among stage 0-II patients (OR = 0.59, 95%CI: 0.35-0.98). The CRC risk was significantly higher among females with the APE1 Glu allele (OR = 1.41, 95%CI: 1.02-1.96). The APE1 148Glu/-656G haplotype was also associated with a significant CRC risk in females (OR = 1.36, 95%CI: 1.03-1.78).OGG1 and APE1 polymorphisms are associated with stage- and sex-specific risk of CRC in the Taiwanese population.
| S-EPMC4806195 | biostudies-literature
Project description:PurposeAge-related cataract is the leading cause of blindness worldwide. Variants in the EPHA2 gene increase the disease risk, and its knockout in mice causes cataract. We investigated whether age, sex, and genetic background, risk factors for age-related cataract, and Epha2 genotype influence Epha2-related cataract development in mice.MethodsCataract development was monitored in Epha2+/+, Epha2+/-, and Epha2-/- mice (Epha2Gt(KST085)Byg) on C57BL/6J and FVB:C57BL/6J (50:50) backgrounds. Cellular architecture of lenses, endoplasmic reticulum (ER) stress, and redox state were determined using histological, molecular, and analytical techniques.ResultsEpha2-/- and Epha2+/- mice on C57BL/6J background developed severe cortical cataracts by 18 and 38 weeks of age, respectively, compared to development of similar cataract significantly later in Epha2-/- mice and no cataract in Epha2+/- mice in this strain on FVB background, which was previously reported. On FVB:C57BL/6J background, Epha2-/- mice developed severe cortical cataract by 38 weeks and Epha2+/- mice exhibited mild cortical cataract up to 64 weeks of age. Progression of cataract in Epha2-/- and Epha2+/- female mice on C57BL/6J and mixed background, respectively, was slower than in matched male mice. N-cadherin and β-catenin immunolabeling showed disorganized lens fiber cells and disruption of lens architecture in Epha2-/- and Epha2+/- lenses, coinciding with development of severe cataracts. EPHA2 immunolabeling showed intracellular accumulation of the mutant EPHA2-β-galactosidase fusion protein that induced a cytoprotective ER stress response and in Epha2+/- lenses was also accompanied by glutathione redox imbalance.ConclusionsBoth, Epha2-/- and Epha2+/- mice develop age-related cortical cataract; age as a function of Epha2 genotype, sex, and genetic background influence Epha2-related cataractogenesis in mice.
| S-EPMC8431977 | biostudies-literature
Project description:Polymorphisms of DNA repair enzymes which may influence their repair efficiency lead to diseases, for example, senile cataract. In this study, we aimed to analyze the association of single nucleotide polymorphisms in AP endonuclease-1 (APE1), 8-oxoguanine glycosylase-1 (OGG1) and X-ray repair cross-complementing-1 (XRCC1) genes with the risk of age-related cataract in a Chinese population. Genotyping was carried out by the polymerase chain reaction and DNA sequencing on 402 cataract patients and 813 controls in this study. Differences in the frequencies were estimated by the chi-square test, and risk was estimated using unconditional logistic regression after adjusting for age and gender. Our results demonstrated there was a significant difference between the case and control groups in the APE1-141 G/G genotype (P=0.002). This difference still existed after adjusting for age and gender (P*=0.003). The APE1-141 T/T genotype and T allele frequencies were significantly higher in cataract patients, while the G/G genotype and G allele frequencies in patients were significantly lower than in controls (P < 0.05). The APE1-141 G/G genotype (OR, 0.49; 95% CI, 0.31-0.77) seems to have a protective role against cataract, and the T allele seems to have a deleterious role in the development of cataract. In OGG1 Ser326Cys and XRCC1 Arg399Gln polymorphisms, there were no significant differences in frequencies of the variant homozygous in patients compared with controls.
| S-EPMC4730093 | biostudies-literature