title: Association analyses of endothelial nitric oxide synthase gene polymorphisms in essential hypertension.
abstract: Endothelial nitric oxide synthase (eNOS), encoded by NOS3, is a potent regulator of vasomotor tone and peripheral resistance. Congenic experiments indicate that a chromosomal segment containing the rat eNOS gene contributes to rat spontaneous hypertension (HT). A role for NOS3 in onset of essential hypertension (HT) is, however, controversial. We therefore decided to test NOS3 polymorphisms in a set of patients who have an accentuated ability to show an existing genetic association. The 112 HT subjects had two HT parents and the normotensive (NT) subjects had two NT parents. All were Anglo-Celtic whites. The two most promising polymorphisms, viz, a biallelic variable number of tandem repeats (VNTR) in intron 4 and an exon 7 variant that leads to an amino acid change (Glu298Asp), were genotyped by PCR (and BanII digestion in the case of the latter). Frequency of the minor allele of the VNTR was 0.11 in the NT and 0.10 in the HT subjects (P = .9). For the exon 7 variant, Asp298 frequency was 0.30 and 0.32 in each respective group (P = .6). Tracking was seen for the Asp298 allele with elevation in body mass index (P = .034), and the minor allele of the VNTR with elevation in LDL (P = .007) and reduction in HDL (P = .048). In conclusion, we saw no association of NOS3 markers with HT in the population studied. However, possible genotypic effects on plasma lipids and body mass index might warrant further studies, especially in view of possible associations with heart disease.
authors.affiliation: Department of Physiology and Institute for Biomedical Research, The University of Sydney, New South Wales, Australia.
authors.forename: A V
authors.initials: AV
authors.lastname: Benjafield
authors.forename: B J
authors.initials: BJ
authors.lastname: Morris
mesh_terms: D000483:Alleles; D015992:Body Mass Index; D015331:Cohort Studies; D005091:Exons / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008077:Lipoproteins, LDL / Q000097:blood; D018598:Minisatellite Repeats; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D011110:Polymorphism, Genetic
chemical_list: D008077:Lipoproteins, LDL; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III