The Interaction Between Endothelial Nitric Oxide Synthase Gene Variants and Hypertension in Relation to Primary Open-Angle Glaucoma

Abstract

To evaluate the interaction between nitric oxide synthase gene (NOS3) variants and hypertension in relation to primary open-angle glaucoma (POAG). Two functional single nucleotide polymorphisms (SNPs)( T-786C: rs2070744, Glu298Asp: rs1799983) and three tagging SNPs (rs7830; rs3918188; rs1800779) were evaluated in nested case-control studies from the Nurses’ Health Study (followed 1980 - 2002) and the Health Professionals’ Follow-up Study (followed 1986 - 2002). Participants were aged ≥ 40 years and Caucasian. Hypertension was defined as ever having had a diagnosis of hypertension; this information has been updated from baseline to 2002 in both cohorts. We included 527 incident cases and 1543 controls, matched on cohort, age and eye exam at the matched cases’ diagnosis dates. Cohort-specific relative risks (RR) were estimated using multivariable conditional logistic regression and pooled with meta-analysis. Hypertension was not associated with POAG. We observed significant interactions between the promoter T-786C SNP and hypertension in relation to overall POAG (p for interaction = 0.02): among those with the genotype TT, hypertension was significantly adversely associated with risk of POAG (RR=1.45, 95% CI = 1.01, 2.08). However, among those carrying the variant allele (C), hypertension was not associated with POAG risk (RR=1.23, [95% CI 0.82, 1.86] for those without hypertension, RR=1.12, [95% 0.80, 1.57] for those with hypertension). Similar interactions were observed with the SNP rs1800779. Interactions were observed between hypertension and NOS3 SNPs in relation to risk of POAG.

Keywords: Clinical (Human) Or Epidemiologic Studies, Natural History, Genetics, Nitric Oxide