Association of the endothelial nitric oxide synthase gene polymorphism with risk of coronary artery disease and myocardial infarction in middle-aged men.
Nitric oxide (NO), formed by endothelial constitutive nitric oxide synthase (eNOS) maintains endothelium-dependent vasodilatation and also mediates antithrombotic actions. The eNOS gene harbours a common polymorphism in intron 4 (4a/b), and some clinical studies have suggested an association of the rare a-allele with coronary artery disease (CAD) and myocardial infarction (MI). However, contradictory results have also been reported. We studied associations of eNOS polymorphism with CAD and MI in two prospective autopsy series comprising altogether 700 Caucasian Finnish men, who died suddenly. In ANCOVA, no significant differences in areas of atherosclerotic lesions and coronary stenosis percentages were found between men carrying the a-allele (ba+aa) compared with those homozygous for the b-allele. Subjects with the a-allele had significantly lower risk of MI (odds ratio 0.44, 95% confidence interval 0.25-0.77, P=0.004) compared with those carrying the bb genotype. Men with the a-allele also tended to have coronary thrombosis less often (odds ratio 0.43, 95% confidence interval 0.18-1.01, P=0.055). The eNOS gene 4a/b polymorphism was not associated with the extent of coronary atherosclerosis, but the a-allele of the variant seems to protect to some degree against the development of MI.
Kunnas
Tarja A
TA
Department of Forensic Medicine, Medical School, University of Tampere, Tampere, Finland. tarja.kunnas@uta.fi
Ilveskoski
Erkki
E
Niskakangas
Tero
T
Laippala
Pekka
P
Kajander
Olli A
OA
Mikkelsson
Jussi
J
Goebeler
Sirkka
S
Penttilä
Antti
A
Perola
Markus
M
Nikkari
Seppo T
ST
Karhunen
Pekka J
PJ
D000328:Adult; D000368:Aged; D000483:Alleles; D003324:Coronary Artery Disease / Q000201:enzymology / Q000235:genetics*; D003328:Coronary Thrombosis / Q000235:genetics / Q000401:mortality; D003645:Death, Sudden; D004730:Endothelium, Vascular / Q000201:enzymology*; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics* / Q000401:mortality; D019001:Nitric Oxide Synthase / Q000235:genetics*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D014505:Urban Population
D019001:Nitric Oxide Synthase