Coronary artery disease and endothelial nitric oxide synthase and angiotensin-converting enzyme gene polymorphisms.
Nitric oxide (NO) inhibits platelet aggregation, proliferation of vascular smooth muscle cells, and leukocyte adhesion to endothelial cells. Thus, genetic variation in or near NO synthase may be involved in the pathogenesis of coronary artery disease (CAD). We investigated the association between CAD and endothelial constitutive NO synthase (ecNOS) and angiotensin-converting enzyme (ACE) gene polymorphisms by polymerase chain reaction analysis. These genotypes were examined in consecutive patients with CAD (n = 40) and control subjects (n = 34). The frequency of ecNOS genotypes in the CAD group (4a/a + 4a/b: 48%; 4bb: 52%) did not differ from that in the control group (4a/a + 4a/b: 29%; 4bb: 71%). The allele frequencies of ecNOS4a and ecNOS4b also did not differ between the two groups. On the other hand, the frequency of the ACE DD genotype in the CAD group (DD: 45%; ID: 35%; II: 20%) was significantly higher than that in the control group (DD: 21%; ID: 35%; II: 44%). The frequency of the D allele in patients with CAD (0.63) was also significantly higher than in controls (0.38). Combined analysis showed that the frequency of the ecNOS genotypes in ACE DD genotype subjects (4a/a + 4a/b: 39%; 4b/b: 61%) in the CAD group was not significantly different from that in the control group (4a/a + 4a/b: 29%; 4b/b: 71%). The ACE genotype might be a predictor of CAD, while the ecNOS genotype appeared to confer no appreciable increase in the risk of CAD.
Nakagami
H
H
Department of Cardiology, Jichi Medical School, Minamikawachi, Tochigi, Japan.
Ikeda
U
U
Maeda
Y
Y
Yamamoto
K
K
Hojo
Y
Y
Kario
K
K
Kuroki
S
S
Shimada
K
K
D016022:Case-Control Studies; D003327:Coronary Disease / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic
C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A