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Polymorphisms of DNA repair genes OGG1 and XPD and the risk of age-related cataract in Egyptians.

ABSTRACT: PURPOSE: To 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. METHODS: This 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 Ser³²?Cys was carried out by PCR including confronting two-pair primers. RESULTS: The 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(³²? 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 Cys³²? allele was also significantly associated with cortical cataract (OR = 2.45, 95% CI = 1.30-4.63, p = 0.005). CONCLUSIONS: The results suggest that the Asn/Asn genotype and Asn³¹² allele of XPD polymorphism, as well as the Cys/Cys genotype and Cys³²? allele of the OGG1 polymorphism, may be associated with increased risk of the development of ARC, particularly the cortical type, in the Egyptian population.

SUBMITTER: Gharib AF

PROVIDER: S-EPMC4029483 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Polymorphisms of DNA repair genes OGG1 and XPD and the risk of age-related cataract in Egyptians.

Gharib Amal F AF Dabour Sherif A SA Etewa Rasha L RL Fouad Rania A RA

Molecular vision 20140521

<h4>Purpose</h4>To 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.<h4>Methods</h4>This 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-p ...[more]

PMID: 24868140

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Project description:OBJECTIVE: This meta-analysis aimed to determine the relationships between XRCC1 Arg399Gln (rs25487 G>A) and XPD Lys751Gln (rs1052559 A>C) polymorphisms and susceptibility to age-related cataract. METHODS: Medline (1966-2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980-2013), CINAHL (1982-2013), Web of Science (1945-2013) and the Chinese Biomedical Database (CBM; 1982-2013) were searched without language restrictions. Various combinations of the keywords and MeSH terms were used to screen for potentially relevant studies, specifically "genetic polymorphisms" or "SNPs" or "variation" or "single nucleotide polymorphism" or "polymorphism" or "mutation" or "variant"; "X-ray repair cross complementing protein 1" or "Xeroderma Pigmentosum Group D Protein" or "X-ray repair cross complementing protein 1" or "Xeroderma Pigmentosum Group D Protein" or "XPD" or "Xeroderma Pigmentosum Complementation Group D Protein" or "ERCC2" or "XRCC1" or "XRCC1 DNA repair protein"; and "Cataract" or " Membranous Cataract" or " Pseudoaphakia." Meta-analyses were conducted using Stata 12.0 software. Crude odds ratios (ORs) and their corresponding 95% confidence intervals (95% CI) were calculated. RESULTS: Six independent case-control studies were included in the meta-analysis. Our results indicated that the association between the genetic polymorphisms of XRCC1 Arg399Gln G>A and XPD Lys751Gln A>C and increased susceptibility to age-related cataracts was statistically significant (XRCC1 Arg399Gln: OR=1.30, 95% CI=1.17-1.44, p<0.001; XPD Lys751Gln: OR=1.25, 95% CI=1.12-1.40, p<0.001, respectively). Ethnicity-stratified analysis indicated that the XRCC1 Arg399Gln G>A polymorphism was correlated with the development and progression of age-related cataract in China, India, and Turkey in the allele model and the dominant model. For the XPD Lys751Gln A>C variant, the association with the pathogenesis of age-related cataract in China and Turkey in the allele model and the dominant model was investigated. CONCLUSIONS: The association of XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms with age-related cataract susceptibility observed in our meta-analyses supports the view that XRCC1 and XPD may play important roles in susceptibility to age-related cataract.

Project description:Age-related cataract (ARC) is a leading cause of visual impairment and blindness worldwide. DNA damage and malfunction of DNA repair are believed to contribute to the pathogenesis of ARC. Aside from increasing age, the risk factors for ARC appear to be rather complex, and one or more gene variations could play critical roles in the diverse processes of ARC progression. This study aimed to investigate the combined effects of different genetic variants on ARC risk.A cohort of 789 ARC patients and 531 normal controls from the Jiangsu Eye Study was included in this study. Genotyping of 18 single-nucleotide polymorphisms (SNPs) in 4 DNA damage/repair genes was performed using TaqMan SNP assays. SNP-SNP interactions were analyzed via multifactor dimensionality reduction (MDR), classification and regression tree (CART) and genetic risk score (GRS) analyses.Based on single-locus analyses of the 18 SNPs examined, WRN-rs11574311 (T>C) was associated with ARC risk. However, in MDR, the gene-gene interaction among the five SNPs (WRN-rs4733220 (G>A), WRN-rs1801195 (T>G), OGG1-rs2072668 (G>C) and OGG1-rs2304277 (A>G)) on ARC risk was significant (OR = 5.03, 95% CI: 3.54~7.13). CART analyses also revealed that the combination of five SNPs above was the best polymorphic signature for discriminating between the cases and the controls. The overall odds ratio for CART ranged from 4.56 to 7.90 showing an incremental risk for ARC. This result indicated that these critical SNPs participate in complex interactions. The GRS results showed an increased risk for ARC among individuals with the SNPs in this polymorphic signature.The use of multifactorial analysis (or an integrated approach) rather than a single methodology could be an improved strategy for identifying complex gene interactions. The multifactorial approach used in this study has the potential to identify complex biological relationships among ARC-related genes and processes. This approach will lead to the discovery of novel biological information, ultimately improving ARC risk management.

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.

Project description:BackgroundPolymorphisms in DNA repair genes have been associated to repair DNA lesions, and might contribute to the individual susceptibility to develop different types of cancer. Nucleotide excision repair (NER), base excision repair (BER), and double-strand break repair (DSBR) are the main DNA repair pathways. We investigated the relationship between polymorphisms in two NER genes, XPC (poly (AT) insertion/deletion: PAT-/+) and XPD (Asp312Asn and Lys751Gln), the BER gene XRCC1 (Arg399Gln), and the DSBR gene XRCC3 (Thr241Met) and the risk of developing lung cancer.MethodsA hospital-based case-control study was designed with 516 lung cancer patients and 533 control subjects, matched on ethnicity, age, and gender. Genotypes were determined by PCR-RFLP and the results were analysed using multivariate unconditional logistic regression, adjusting for age, gender and pack-years.ResultsBorderline association was found for XPC and XPD NER genes polymorphisms, while no association was observed for polymorphisms in BER and DSBR genes. XPC PAT+/+ genotype was associated with no statistically significant increased risk among ever smokers (OR = 1.40; 95%CI = 0.94-2.08), squamous cell carcinoma (OR = 1.44; 95%CI = 0.85-2.44), and adenocarcinoma (OR = 1.72; 95%CI = 0.97-3.04). XPD variant genotypes (312Asn/Asn and 751Gln/Gln) presented a not statistically significant risk of developing lung cancer (OR = 1.52; 95%CI = 0.91-2.51; OR = 1.38; 95%CI = 0.85-2.25, respectively), especially among ever smokers (OR = 1.58; 95%CI = 0.96-2.60), heavy smokers (OR = 2.07; 95%CI = 0.74-5.75), and adenocarcinoma (OR = 1.88; 95%CI = 0.97-3.63). On the other hand, individuals homozygous for the XRCC1 399Gln allele presented no risk of developing lung cancer (OR = 0.87; 95%CI = 0.57-1.31) except for individuals carriers of 399Gln/Gln genotype and without family history of cancer (OR = 0.57; 95%CI = 0.33-0.98) and no association was found between XRCC3 Thr241Met polymorphism and lung cancer risk (OR = 0.92; 95%CI = 0.56-1.50), except for the 241Met/Met genotype and squamous cell carcinoma risk (OR = 0.47; 95%CI = 0.23-1.00).ConclusionIn conclusion, we analysed the association between XPC, XPD, XRCC1, and XRCC3 polymorphisms and the individual susceptibility to develop lung cancer in the Spanish population, specifically with a highly tobacco exposed population. We attempt to contribute to the discovery of which biomarkers of DNA repair capacity are useful for screening this high-risk population for primary preventing and early detection of lung cancer.

Dataset Information

Polymorphisms of DNA repair genes OGG1 and XPD and the risk of age-related cataract in Egyptians.

Publications

Polymorphisms of DNA repair genes OGG1 and XPD and the risk of age-related cataract in Egyptians.

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