Polymorphisms rs693421 and rs2499601 at locus 1q43 and their haplotypes are not associated with primary open-angle glaucoma: a case–control study

Abstract

Objective: The genetic spectrum of primary open-angle glaucoma (POAG) in middle-eastern Saudi's is still elusive. To this end, we investigated an association between rs693421, rs2499601 and their haplotypes at chromosome 1q43 locus with POAG and its related clinical phenotypes. Genotyping was performed with TaqMan ® assays. Haplotypes and their interaction analysis were carried out by SHEsis and SNPStats online tools. Results: The minor "T" allele frequency of rs693421 was 0.48 in controls and 0.52 in cases (odds ratio (OR) = 1.15, 95% confidence interval (CI) 0.85-1.54, p = 0.368). Similarly, for rs2499601, the minor "C" allele frequency was 0.49 in controls as compared to 0.53 in cases (OR = 1.19, 95% CI 0.89-1.60, p = 0.236). Besides, genotype distribution for both these polymorphisms was also not significant in additive, dominant and recessive models. rs693421 and rs2499601, showed significant linkage disequilibrium (D' statistics = 0.69, p < 0.001) but haplotype association was non-significant (p = 0.698). The significance did not vary after adjustment to age and sex. No significant genotype association was observed with intraocular pressure, cup/disc ratio and number of anti-glaucoma medication in POAG group. Furthermore, age, sex and genotypes did not contribute any significant risk of POAG in regression analysis. We report no association between rs693421, rs2499601 and their haplotypes with POAG and related phenotypes.

Association of endothelial nitric oxide synthase (NOS3) gene polymorphisms with primary open-angle glaucoma in a Saudi cohort

“…Our study shows that NOS3 polymorphism rs1799983 (894T allele) is a significant risk factor for POAG and that haplotypes CG and CT of rs2070744 and rs1799983 can significantly modulate the risk of POAG, particularly among men only. Except for rs10483727 in the SIX1/ SIX6 [45], this finding is in contrast to the lack of association previously reported in our similar cohort studies in Saudi POAG patients [25][26][27][28][46][47][48][49] in the genetic loci that significantly influenced POAG or its endophenotypes in other ethnicities [3]. NOS3 codes for NO derived from vascular endothelium.…”

“…Besides, a recent meta-analysis also showed that polymorphisms rs1799983 and rs2070744 in NOS3 play a significant role in modulating the risk of POAG [24]. We have recently reported negative association of polymorphisms in TMTC2 (rs7961953) [25], PLXDC2 (rs7081455) [26], ATOH7 (rs7916697) [27] and at locus 1q43 [28]. The aim of the present study is to investigate the effects of NOS3 variants on the risk of POAG and determine the association between NOS3 polymorphisms (and haplotypes) and POAG patients of Saudi origin.…”