Y. Shimasaki et al., ASSOCIATION OF THE MISSENSE GLU298ASP VARIANT OF THE ENDOTHELIAL NITRIC-OXIDE SYNTHASE GENE WITH MYOCARDIAL-INFARCTION, Journal of the American College of Cardiology, 31(7), 1998, pp. 1506-1510
Objectives. We examined the possible association between the missense
Gln298Asp variant of the endothelial nitric oxide synthase (eNOS) gene
and myocardial infarction (MI). Background. Endothelium-derived nitri
c oxide (NO) plays a key role ire the regulation of vascular tone. Rec
ently, we reported that a missense Glu298Asp variant in exon 7 of the
eNOS gene is a possible genetic factor involved in the pathogenesis of
coronary spasm. Endothelium-derived NO also has vasoprotective effect
s by suppressing platelet aggregation, leukocyte adhesion anal smooth
muscle cell proliferation. Methods. We screened 285 patients with an M
I and 607 control subjects in Kumamoto Prefecture, Japan. Genotypes we
re determined by polymerase chain reaction-restriction fragment-length
polymorphism analysis. Results. The frequency of the missense Glu298A
sp variant was significantly higher in the MI group than in the contro
l group (21.1% vs. 13.3%, p = 0.003, odds ratio 1.73 for the dominant
effect of the eNOS T allele). Multiple logistic regression analysis sh
owed that the missense Glu298Asp variant was an independent risk facto
r for MI, as was diabetes mellitus, hypertension, cigarette smoking, h
ypercholesterolemia and body mass index. Conclusions. There was a sign
ificant association of the mis-sense Glu298Asp variant of the eNOS gen
e with MI. This marker-disease association may be doe to the impaired
effects of NO on the cardiovascular system: dysregulation of vascular
tone, platelet aggregation and leukocyte adhesion and smooth muscle ce
ll proliferation, all of which promote coronary atherosclerosis and th
rombosis. (C) 1998 by the American College of Cardiology.