☆ 4.3 Article

Association of Ornithine Transcarbamylase Gene Polymorphisms With Hypertension and Coronary Artery Vasomotion

AMERICAN JOURNAL OF HYPERTENSION (2009)

Journal

AMERICAN JOURNAL OF HYPERTENSION

Volume 22, Issue 9, Pages 993-1000

Publisher

OXFORD UNIV PRESS

DOI: 10.1038/ajh.2009.110

Keywords

Funding

Conseil Regional Nord-Pas-de-Calais
Institut National de la Sante et de la Recherche Medicale (Inserm).
Ministere de I'Enseignement Superieur et de la Recherche Scientifique, Algeria
Centre National des Oeuvres Universitaires et Scolaires.
Alzheimer's association [IIRG-06-25487]
France Alzheimer Association
Conseil Regional du Nord-Pas de Calais
Fondation pour la Recherche Medicale, ONIVINS
Parke-Davis Laboratory
Mutuelle Generale de I'Education Nationale
Reseau National de Sante Publique
Direction Generale de La Sante, Inserm
Institut Pasteur de Lille
Universite de Lille 2
Unite d'Evaluation du Centre Hospitalier et Universitaire de Lille (France).
EISAI Co (France).
Direction de la Recherche et des Etudes Doctorales de Lille
Centre Hospitalier Universitaire de Lille, Inserm,
Institut Pasteur de Lille (France).

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Abstract

BACKGROUND Previous studies have suggested that the activity of enzymes involved in the urea cycle may modulate nitric oxide (NO) production, arterial vasomotion, and hypertension. Our aim was to determine whether hypertension and coronary vasomotion could be associated with polymorphisms within the ornithine transcarbamylase (OTC) gene, located on chromosome X and coding for a key-enzyme of the urea cycle. METHODS Among 11 OTC polymorphisms that were originally selected from databases, the tag single-nucleotide polymorphism (SNP) rs5963409 and the independent SNP rs1800321 were tested for association with hypertension in two independent population samples recruited in Northern (Multinational MONItoring of and determinants in CArdiovascular disease (MONICA) study, n = 1,138) and Western (Etude du Vieillissement Arteriel (EVA) study, n = 1,166) France. The vasomotor response of coronary arteries to methylergonovine maleate and isosorbide dinitrate was also evaluated in an independent sample (the vasomotion study, n = 121). RESULTS In males, the frequency of the rs5963409 minor allele was consistently higher in hypertensive (HT) than in normotensive subjects in the MONICA and EVA studies. In the combined sample, the rs5963409 minor allele was associated with an increased risk of hypertension (odds ratio (OR) (95% confidence interval (CI)) = 1.45 (1.10-1.90); P = 0.008). This association was independent of classical confounding factors. Consistently, rs5963409 minor allele was associated with a greater susceptibility to vasoconstriction in response to methylergonovine maleate (P = 0.0072). In contrast, no significant association between rs5963409 and hypertension could be detected in females. CONCLUSION Our results suggest that the OTC rs5963409 polymorphism may be associated with hypertension and coronary vasomotion in males. Am J hypertens 2009; 22:993-1000 (C) 2009 American Journal of Hypertension, Ltd.

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