Coronary artery spasm and the polymorphisms of the endothelial nitric oxide synthase gene.
BACKGROUND
Coronary artery spasm plays an important role in the pathogenesis of vasospastic angina, and contributes to the development of several acute coronary syndromes. Endothelial nitric oxide synthase (ecNOS) catalyzes the synthesis of nitric oxide, which regulates vascular tone, and may be related to coronary vasospasm. The present study investigated whether coronary spasm is related to particular polymorphisms of the ecNOS gene.


RESULTS
Spasm provocation by serial infusions of acetylcholine was performed on 165 patients who were clinically suspected of having angina. In both study patients and healthy controls (n=400), genomic polymorphisms of the ecNOS gene were determined by using polymerase chain reaction. Quantitative luminal diameter measurements of the 3 major coronary arteries were initially obtained before and after acetylcholine injection, and then after isosorbide dinitrate injection, by using a computer-assisted analysis system. Logistic multiple regression analysis identified the a/a or a/b genotype in intron 4 of ecNOS (NOS4a: p=0.0431, odds ratio (OR) 2.43) and diabetes mellitus (p=0.0060, OR 4.88) as significant predictors of coronary spasm. In the patients with NOS4a, both the induced and spontaneous contractions were augmented.


CONCLUSIONS
The present study results indicated that NOS4a could be a good marker for coronary artery spasm.
Kaneda
Hideaki
H
Department of Cardiovascular Medicine, The University of Tokyo, Japan.
Taguchi
Junichi
J
Kuwada
Yukihiro
Y
Hangaishi
Misako
M
Aizawa
Toru
T
Yamakado
Minoru
M
Ogasawara
Ken
K
Aizawa
Tadanori
T
Ohno
Minoru
M
D000109:Acetylcholine; D000368:Aged; D015415:Biomarkers / Q000097:blood; D017023:Coronary Angiography; D003329:Coronary Vasospasm / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D004234:Diuretics, Osmotic / Q000008:administration & dosage; D005260:Female; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D007547:Isosorbide / Q000008:administration & dosage; D007564:Japan; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D052250:Nitric Oxide Synthase Type III / Q000097:blood / Q000235:genetics* / Q000502:physiology; D009573:Nitrites / Q000097:blood; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D014665:Vasodilator Agents / Q000008:administration & dosage
D015415:Biomarkers; D004234:Diuretics, Osmotic; D009566:Nitrates; D009573:Nitrites; D014665:Vasodilator Agents; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine; D007547:Isosorbide