Genetic polymorphisms in DNA repair genes OGG1, APE1, XRCC1, and XPD and the risk of age-related cataract.

PURPOSE: To analyze the association of the polymorphisms in 8-oxoguanine glycosylase-1 (OGG1), X-ray repair cross-complementing-1 (XRCC1), and AP endonuclease-1 (APE1) genes in the base excision repair pathway and xeroderma pigmentosum complementation group D (XPD) in the nucleotide excision repair pathway with the risk of cataract in a Chinese population.

DESIGN

Case-control study.

PARTICIPANTS

Subjects with cataract (n = 415) or no cataract (n = 386) in the Age Related Eye Disease Ancillary Study.

METHODS

The study included 415 cataract patients and 386 controls. Genotyping was carried out by the polymerase chain reaction-restriction fragment length polymorphism method. Differences in the frequencies were estimated by the chi-square test, and risk was estimated by using unconditional logistic regression after adjusting for age and gender.

MAIN OUTCOME MEASURES: Association of single nucleotide polymorphisms in OGG1-Ser326Cys with the development of age-related cataract.

RESULTS

The OGG1 Cys/Cys genotype frequency was significantly higher in cataract patients (P = 0.014; odds ratio [OR], 2.06; 95% confidence interval [CI], 1.171-3.624). The OGG1 Ser/Ser genotype (P = 0.003; OR, 0.647; 95% CI, 0.487-0.860) seems to have a protective role against cataract, and the Cys allele (P<0.001; OR, 1.517; 95% CI, 1.204-1.911) seems to have a deleterious role in the development of cataract. The genotype frequency of the Ser/Ser of OGG1-Ser326Cys was significantly different in the cortical and mixed-type cataract group (P = 0.014; OR, 0.591; 95% CI, 0.391-0.893; and P = 0.035; OR, 0.639; 95% CI, 0.425-0.960; respectively), and the Cys/Cys genotype of OGG1-Ser326Cys was significantly different in the mixed-type cataract group (P = 0.012; OR, 2.610; 95% CI, 1.284-5.306) compared with that of healthy controls. In XRCC1-Arg399Gln, APE1-Asp148Glu, and XPD-Lys751Gln polymorphisms, there were no significant differences in frequencies of the variant homozygous in patients compared with controls.

CONCLUSIONS

Results suggest that the Cys/Cys genotype of the OGG1-Ser326Cys polymorphism may be associated with increased risk of age-related cataract. However, in XRCC1-Arg399Gln, APE1-Asp148Glu, and XPD-Lys751Gln polymorphisms, there were no significant differences in frequencies of the variant homozygous in patients compared with controls.