Endothelial nitric oxide synthase gene polymorphism and acute myocardial infarction.
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 (>/=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.
Hibi
K
K
From the Second Department of Internal Medicine and the Department of Public Health, Yokohama City University School of Medicine, Japan. hibikiyo@yellow.med.yokohama-cu.ac.jp
Ishigami
T
T
Tamura
K
K
Mizushima
S
S
Nyui
N
N
Fujita
T
T
Ochiai
H
H
Kosuge
M
M
Watanabe
Y
Y
Yoshii
Y
Y
Kihara
M
M
Kimura
K
K
Ishii
M
M
Umemura
S
S
D016022:Case-Control Studies; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D009569:Nitric Oxide / Q000235:genetics*; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D017354:Point Mutation; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index
D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III