Synergistic interaction of T-786-->C polymorphism in the endothelial nitric oxide synthase gene and smoking for an enhanced risk for coronary spasm.
OBJECTIVE
We previously reported that a T-786-->C polymorphism in the 5'-flanking region of the endothelial nitric oxide synthase gene and smoking were independently associated with coronary spasm; however, the interaction between this polymorphism and smoking remains to be elucidated.


METHODS
We analyzed 209 men and 238 women who were admitted consecutively at our institution; all subjects received an intracoronary injection of acetylcholine (ACh) while undergoing coronary angiography for evaluation of chest pain: all subjects had no significant coronary stenosis. We divided these subjects into four groups: non-smokers with T/T genotype (Control Group A); non-smokers with C/T or C/C genotype (Group B); smokers with T/T genotype (Group C); and smokers with C/T or C/C genotype (Group D). We further examined quantitative coronary angiographies of the left anterior descending coronary artery in a subset of 54 consecutive men and 53 consecutive women.


RESULTS
The frequencies of coronary spasm in Group B (male: 61%, female: 78%), Group C (62%, 59%) and Group D (91%, 92%) were significantly higher than in Group A (30%, 38%). In the males, ACh-induced vasoconstriction was greatest in Group D, and the change was weakest in Group A. In the females, ACh-induced vasoconstrictions were significantly greater in Groups B, C and D than in Group A. The T-786-->C polymorphism and smoking combine to increase the risk of coronary spasm.
Department of Cardiovascular Medicine, Graduate School of Medical Sciences. Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
Masafumi
M
Nakayama
Michihiro
M
Yoshimura
Tomohiro
T
Sakamoto
Yukio
Y
Shimasaki
Shota
S
Nakamura
Teruhiko
T
Ito
Koji
K
Abe
Megumi
M
Yamamuro
Yoshihiro
Y
Miyamoto
Yoshihiko
Y
Saito
Kazuwa
K
Nakao
Hirofumi
H
Yasue
Hisao
H
Ogawa
D000109:Acetylcholine / Q000494:pharmacology; D000368:Aged; D044466:Asian People; D001483:Base Sequence / Q000235:genetics; D003329:Coronary Vasospasm / Q000235:genetics*; D005260:Female; D006801:Humans; D007548:Isosorbide Dinitrate / Q000494:pharmacology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D019001:Nitric Oxide Synthase; D007548:Isosorbide Dinitrate; D000109:Acetylcholine