Association Analysis of Variants Rs35934224 in and Rs6478746 in in Primary Angle-closure and Pseudoexfoliation Glaucoma

Objective: Previous genome-wide studies have demonstrated significant pathogenic association between variants rs35934224 within and rs6478746 near in primary open-angle glaucoma. We investigated the association between these variants in primary angle-closure glaucoma (PACG) and pseudoexfoliation glaucoma (PXG) patients of Saudi origin.

Methods: In a case-control study, DNA samples from 249 controls (135 men and 114 women), 100 PACG cases (44 men and 56 women), and 95 PXG cases (61 men and 34 women) were genotyped by TaqMan based real-time PCR. Statistical tests were performed to evaluate genetic association with glaucoma types and related clinical indices.

Results: The allele frequencies of rs35934224 and rs6478746 did not show significant variation in PACG and PXG than controls, except that the rs35934224[T] allele was found to be significantly low among PXG women (0.10) as compared to controls (0.21) (odds ratio = 0.38, 95% confidence interval = 0.16-0.94,  = 0.024). Rs35934224 genotypes showed a nominal-to-borderline protective association with PACG and PXG among women in different genetic models. However, except for the over-dominant model in PACG ( = 0.0095), none of the effects survived Bonferroni's correction ( < 0.01). Rs6478746 showed no significant genotype or allelic association with PACG and PXG. Regression analysis showed no influence on disease outcome, and neither showed any correlation with intraocular pressure and cup/disk ratio in both PACG and PXG.

Conclusions: Variants rs35934224 in and rs6478746 near are not associated with PACG and PXG in the Saudi cohort, but rs35934224 may confer modest protection among women. Further population-based studies are needed to validate these results.