title: Lack of association between common endothelial nitric oxide synthase gene haplotypes and left ventricular hypertrophy in hypertension.
abstract: The endothelial nitric oxide synthase (NOS3) gene has been implicated in the pathogenesis of hypertension-related left ventricular hypertrophy (LVH). Candidate-gene studies have examined the role of NOS3 variation, but reported results are inconsistent. In this study, we investigated the association of three clinically relevant polymorphisms (promoter T786C, intronic 4a/b, and nonsynonymous G894T) in a case-control sample of 230 ethnically homogeneous (Caucasians) patients with essential hypertension, with (n = 64) and without (n = 166) clinically diagnosed LVH. Haplotype analysis was also performed. In single-marker analyses, no significant associations with LVH were detected by univariate and multivariate regression models. In the haplotype-based association analysis, no common haplotype was associated with the development of LVH. A rare haplotype consisting of the three mutant alleles (C-a-T*) was found to be present only in patients with LVH (3.4%) and not in control hypertensive patients. Despite the biological rationale for the involvement of the NOS3 gene in LVH, no evidence for a major role of common NOS3 haplotypic variation was found. Considering the totality of available evidence, single-gene analyses of the NOS3 gene have not uncovered detectable genetic effects, and pathway-based analyses that examine interactions of multiple loci may be more informative about the complex genetic etiology of LVH.
authors.forename: Georgios D
authors.initials: GD
authors.lastname: Kitsios
authors.forename: Ioannis
authors.initials: I
authors.lastname: Stefanidis
authors.forename: Elias
authors.initials: E
authors.lastname: Zintzaras
mesh_terms: D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000150:complications*; D017379:Hypertrophy, Left Ventricular / Q000150:complications* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*
chemical_list: D052250:Nitric Oxide Synthase Type III