XRCC1 and XPD DNA repair gene polymorphisms: a potential risk factor for glaucoma in the Pakistani population.

Purpose: The present study was designed to determine the association of polymorphisms of the DNA repair genes X-ray cross-complementing group 1 (XRCC1) (c.1316G>A [rs25487]) and xeroderma pigmentosum complementation group D (XPD) (c.2298A>C [rs13181]) with primary open-angle glaucoma (POAG) and primary closed-angle glaucoma (PCAG).
Methods: In this prospective case-control study, polymerase chain reaction-restriction fragment length polymorphism analysis was used to study the association of XRCC1 and XPD with 160 POAG patients, 163 PCAG patients, and 193 unaffected controls.
Results: XRCC1 rs25487 was found to be significantly associated specifically with male POAG patients (χ(2) = 13.2 [p = 0.001]), only for the dominant model (odds ratio [OR] = 2.65 [95% confidence interval [CI] = 1.44-4.85], p < 0.005). In addition XPD rs13181 was also found to be associated with male POAG patients (χ(2) = 12.1 [p < 0.005]), for both dominant (OR = 2.44 [95% CI = 1.33-4.47], p < 0.005) as well as recessive model (OR = 3.62 [95% CI = 1.45-9.01], p < 0.01). Combined genotypes of both the genes revealed that the heterozygote AC/GA was significantly associated with the male POAG patients (z = 3.00 [p < 0.001]). The AA/GG genotype was present at a higher frequency in the male controls and the AA/GA in the female controls and could thus have a protective role in males and females, respectively.
Conclusions: We postulate that defects in the DNA repair genes XRCC1 and XPD may possibly be associated with the progression of POAG in male patients of Pakistani origin.