A smoking-dependent risk of coronary artery disease associated with a polymorphism of the endothelial nitric oxide synthase gene.
Endothelium-dependent vasodilatation is mediated by release of nitric oxide formed by constitutively expressed endothelial nitric oxide synthase (ecNOS). We explored the distribution of polymorphism ecNOS4a/b in 549 subjects with, and 153 without, coronary artery disease in relation to smoking. In current and ex-cigarette smokers, but not nonsmokers, there was a significant excess of homozygotes for the rare ecNOS4a allele in patients with severely stenosed arteries, compared with those with no or mild stenosis. This genotype was also associated with a history of myocardial infarction. This smoking-dependent excess coronary risk in ecNOS4a homozygotes is consistent with predisposition to endothelial dysfunction.
Wang
X L
XL
Department of Cardiovascular Medicine, University of New South Wales, Prince Henry/Prince of Wales Hospitals, Sydney, Australia.
Sim
A S
AS
Badenhop
R F
RF
McCredie
R M
RM
Wilcken
D E
DE
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D015331:Cohort Studies; D003327:Coronary Disease / Q000453:epidemiology* / Q000235:genetics*; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000201:enzymology*; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics*; D019001:Nitric Oxide Synthase / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012016:Reference Values; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D016540:Smoking Cessation
D017931:DNA Primers; D019001:Nitric Oxide Synthase