Polymorphisms in two DNA repair genes (XPD and XRCC1) – association with age related cataracts

[摘要] Purpose: Age related cataract is theleading cause of blindness in the world today. The association betweenDNA damage to the lens epithelium and the development of lens opacitieshas been reported in many studies. Polymorphisms of DNA repair enzymesmay affect repair efficiency and thereby lead to the development of agerelated cataract. Methods: In this study, we aimed todetermine the frequency of polymorphisms in two DNA repair enzymegenes, xeroderma pigmentosum complementation group (XPD) codon312 and X-ray complementing group1 (XRCC1) codon 399, in asample of 208 cataract patients (69 with cortical, 69 with nuclear and70 with posterior sub capsular) and 151 sex and age matched healthycontrols. XPD genotype was determined by AmplificationRefractory Mutation System (ARMS) while XRCC1 was genotypedusing the PCR-RFLP method. Results: There was a significantdifference between frequencies for XPD-312 Asn/Asn genotype incataract patients (21.6%) and healthy controls (13.2%; p=0.03, OR=1.97,95% CI=1.06–3.63). Considering the types of cataract, XPD-312Asn/Asn genotype was found to be significantly different in patientswith cortical (29%) type in comparison to controls (13.2%; p=0.03,OR=2.39, 95% CI=1.11–5.12). No statistically significant difference wasfound for the genotypic and allelic distributions of the polymorphismin XRCC1. The MDR interaction analysis revealed weak synergismbetween the markers XPD-Asp312Asn and XRCC1-Arg399Glncontributing to cataract. It also showed that the AA genotype of XPD-Asp312Asnpolymorphism when present in combination with the GA genotype of XRCC1-Arg399Glnhad a fivefold and with AA had a fourfold risk for developing cataract.Conclusions: The present study suggeststhat a polymorphism in XPD codon 312 may be associated with thedevelopment of maturity onset cataract. This is the first report on theassociation of XPD Asp312Asn polymorphism with maturity onsetcataract.

[学科分类] 生物化学/生物物理