Abstract
AimTo investigate the association of endothelial nitric oxide synthase (NOS3) gene polymorphisms in patients with primary open-angle glaucoma (POAG) of Saudi origin.MethodsThis case-control study included 173 patients with POAG (94 men and 79 women) and 171 controls (98 men and 73 women). Genotyping of rs2070744 (T-786C) and rs1799983 (G894T) variants of the NOS3 gene was performed using TaqMan® assay.ResultsRs1799983 genotypes showed a significant association with POAG but did not survive Bonferroni correction (pcorrection = 0.01). The minor ‘T’ allele was significantly associated with the risk of POAG among men (p = 0.025, odds ratio (OR) = 1.77, 95% confidence interval (CI) = 1.07–2.94). Likewise, the genotypes were significantly associated with POAG among men in dominant (p = 0.030, OR = 1.92, 95% CI = 1.06–3.48) and log-additive models (p = 0.022, OR = 1.82, 95% CI = 1.08–3.07), and after adjustment for age and smoking. Genotype and allele frequencies of rs2070744 were not significantly different between POAG cases and controls, and after sex stratification. CG haplotype was significantly protective (p = 0.011, OR = 0.52, 95% CI = 0.32–0.87) and CT haplotype conferred significantly increased risk of POAG (p = 0.016, OR = 2.60, 95% CI = 1.16–5.82) among men. Rs1799983 showed trend (p = 0.054) towards risk of POAG independent of age, gender, smoking, and rs2070744 polymorphism in logistic regression analysis. Both the polymorphisms showed no association with POAG phenotypes such as intraocular pressure and cup/disc ratio.ConclusionOur results suggest that the polymorphism rs1799983 and the haplotypes of rs20707440 and rs1799983 in the NOS3 gene may significantly modulate the risk of POAG in Saudi’s, particularly among men. Further larger studies are needed to confirm these findings.
Highlights
Primary open-angle glaucoma (POAG) is a complex optic neuropathy and a significant cause of permanent blindness worldwide, including in Saudi Arabia [1, 2]
The minor ‘T’ allele was significantly associated with the risk of POAG among men (p = 0.025, odds ratio (OR) = 1.77, 95% confidence interval (CI) = 1.07–2.94)
The genotypes were significantly associated with POAG among men in dominant (p = 0.030, OR = 1.92, 95% CI = 1.06–3.48) and log-additive models (p = 0.022, OR = 1.82, 95% CI = 1.08–3.07), and after adjustment for age and smoking
Summary
Primary open-angle glaucoma (POAG) is a complex optic neuropathy and a significant cause of permanent blindness worldwide, including in Saudi Arabia [1, 2]. Nitric oxide (NO) is an active biological messenger that plays a key role in the regulation of vascular homeostasis and is involved in diverse physiological processes [9]. Variations in eNOS activity influenced by genetic variations and/or environmental factors may play a significant role in POAG pathogenesis. Many studies have reported an association between isoform eNOS-3 (NOS3) gene polymorphisms and risk of POAG with inconsistent findings [19,20,21]. Among the important single nulecotide polymorphisms (SNPs) reported in the NOS3 (OMIM 163729) locus are rs2070744, a T-to-C promoter variant (T-786C) and rs1799983, a G-to-T variant (G894T) at codon 298 in exon 7 (Glu298Asp). A recent meta-analysis showed that polymorphisms rs1799983 and rs2070744 in NOS3 play a significant role in modulating the risk of POAG [24]. The study focused on the promoter polymorphism rs2070744 and the missense polymorphism rs1799983
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