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From the Second Department of Internal Medicine (K.H., S.U., T.I., K.T.,
N.N., T.F., H.O., M.K., Y.W., M.K., K.K., M.I.) and the Department of Public
Health (S.M.), Yokohama City University School of Medicine; and the Department
of Cardiology, Saiseikai Yokohama City Nanbu Hospital (Y.Y.), Yokohama,
Kanagawa, Japan.
Correspondence to Satoshi Umemura, MD, Second Department of Internal Medicine, Yokohama City University School of Medicine, 3–9, Fukuura, Kanazawa-Ku, Yokohama 236, Japan. E-mail hibikiyo{at}yellow.med.yokohama-cu.ac.jp
Abstract—Recently a point mutation
of guanine to thymine at nucleotide position 1917 in
the endothelial nitric oxide synthase (eNOS) gene has
been reported to be associated with coronary artery spasm. In
addition, a significant association of the 4a/b polymorphism in
intron 4 of the eNOS gene with coronary artery disease has been
reported. However, the implications of these polymorphisms with
respect to acute myocardial infarction (AMI) remain to be established.
We conducted a case-control study of 226 patients with AMI and 357
healthy gender- and age-matched control subjects. In the former group,
coronary angiograms were evaluated according to angiographic
criteria based on the number of diseased vessels (
© 1998 American Heart Association, Inc.
Scientific Contributions
Endothelial Nitric Oxide Synthase Gene Polymorphism and Acute Myocardial Infarction
75%) and the
number of stenotic lesions (50%). Homozygosity for the
Glu-Asp298 polymorphism existed in 5 of 226 patients with AMI
(2.2%) but not in any of the 357 control subjects
(P=.0085). However, when we evaluated the
coronary angiograms of 226 case patients, there was no
difference in the number of diseased vessels or the number of
stenotic lesions between the patients with this homozygote and
those without it. By contrast, there was no evidence of a significant
increase in the risk of AMI or the severity of coronary
atherosclerosis among individuals with the a/a
genotype of the eNOS4a/b polymorphism. Our results imply
that patients who are homozygous for the Glu-Asp298 polymorphism
may be genetically predisposed to AMI; however, this mutation
apparently is not related to the severity of coronary
atherosclerosis. Further studies are needed to confirm
our results and characterize the molecular mechanisms by which eNOS is
involved in susceptibility to AMI.
Key Words: endothelium-derived relaxing factor • genes • myocardial infarction • atherosclerosis • angiography
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