Influence of the endothelial nitric oxide synthase gene on conventional and ambulatory blood pressure: sib-pair analysis and haplotype study

A. Persu, W.J. Vinck, O. El Khattabi, R.G.J.H. Janssen, A.D.C. Paulussen, O. Devuyst, R.F.M. Vlietinck, R.H. Fagard

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Abstract

Influence of the endothelial nitric oxide synthase gene on conventional and ambulatory blood pressure: sib-pair analysis and haplotype study.

Persu A, Vinck WJ, Khattabi OE, Janssen RG, Paulussen AD, Devuyst O, Vlietinck R, Fagard RH.

aNephrology Unit, Universite Catholique de Louvain, Brussels bHypertension and Cardiovascular Rehabilitation Unit, Katholieke Universiteit Leuven cCentre for Human Genetics, Katholieke Universiteit Leuven, Leuven, Belgium dCluster of Genetics and Cell Biology, Department of Population Genetics, Maastricht University, Maastricht eNutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht, The Netherlands.

BACKGROUND: Nitric oxide is involved in the regulation of vascular basal tone and blood pressure. Polymorphisms of NOS3, the gene that codes for endothelial nitric oxide synthase, have been associated with essential hypertension. OBJECTIVE: To look for linkage and association of three di-allelic polymorphisms (Glu298Asp, intron 4 VNTR and T-786C) and the intron 13 CA-repeat of NOS3 with blood pressure as a continuous trait. METHODS: Genotyping was performed in 110 dizygotic white twin pairs from Flanders, Belgium. The influence of NOS3 polymorphisms on conventional and ambulatory blood pressure was assessed by sib-pair analysis and haplotype association analysis. RESULTS: Genotype frequencies were similar to those previously reported in white populations. Sib-pair analysis did not show a significant influence of either polymorphism on blood pressure. Haplotype analysis disclosed a significant association between NOS3 haplotypes and daytime ambulatory diastolic (P = 0.02) and systolic (P < 0.0001) blood pressure, the latter remaining significant after multiple testing was taken into account (P = 0.032). The association between daytime ambulatory systolic blood pressure and NOS3 haplotypes was mainly attributable to four haplotypes accounting for 11.9% of all represented haplotypes. CONCLUSION: We show for the first time a highly significant association of ambulatory blood pressure with NOS3 haplotypes in well-characterized white individuals from Flanders. These results pave the way for studies looking for the influence of NOS3 on blood pressure in high-risk subsets such as diabetic or hypertensive patients. They indicate the importance of ambulatory blood pressure and haplotype analysis in revealing the moderate effect of polymorphisms on blood pressure
Original languageEnglish
Pages (from-to)759-765
JournalJournal of Hypertension
Volume23
Issue number4
DOIs
Publication statusPublished - 1 Jan 2005

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