Association of ornithine transcarbamylase gene polymorphisms with hypertension and coronary artery vasomotion.
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 trends and determinants in CArdiovascular disease (MONICA) study, n = 1,138) and Western (Etude du Vieillissement Artériel (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.


CONCLUSIONS
Our results suggest that the OTC rs5963409 polymorphism may be associated with hypertension and coronary vasomotion in males.
Dumont
Julie
J
Inserm, U744, Lille, France.
Meroufel
Djabaria
D
Bauters
Christophe
C
Hansmannel
Franck
F
Bensemain
Faïza
F
Cottel
Dominique
D
Hamon
Martial
M
Lambert
Jean-Charles
JC
Ducimetière
Pierre
P
Amouyel
Philippe
P
Zureik
Mahmoud
M
Brousseau
Thierry
T
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000235:genetics; D003329:Coronary Vasospasm / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D003331:Coronary Vessels / Q000503:physiopathology*; D005260:Female; D005602:France / Q000453:epidemiology; D005787:Gene Frequency; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D009954:Ornithine Carbamoyltransferase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D009954:Ornithine Carbamoyltransferase