The endothelial nitric oxide synthase gene -786T/C polymorphism is a predictive factor for reattacks of coronary spasm.
OBJECTIVE
We previously found a -786T/C polymorphism in the 5'-flanking region of the endothelial nitric oxide synthase (eNOS) gene and reported that this polymorphism is strongly associated with coronary spasm. In this study, we examined whether the polymorphism is a prognostic marker in coronary spasm patients.


RESULTS
We examined the clinical courses of 201 consecutive patients with coronary spasm who were admitted to our institution: 146 patients with the -786T/T genotype; 50 patients with the -786C/T genotype; and five patients with the -786C/C genotype. The mean follow-up period was 76+/-60 months. All the patients took calcium channel blockers and/or nitrate during the follow-up period. In this study, no patients died due to a cardiac event. About 25 patients were readmitted owing to cardiovascular disease. Out of these 25 patients, 23 patients were readmitted owing to a reattack of coronary spasm. The -786C allele was significantly associated with readmission due to coronary spasm (P=0.0072, odds ratio: 3.37 in the dominant effect). Kaplan-Meier analysis revealed that the occurrence of readmission was significantly higher in the patients with the -786C allele than in the patients without the -786C allele (P=0.0079). Further, multiple logistic regression analysis revealed that the -786T/C polymorphism was an independent predictor for readmission due to reattack of coronary spasm (P=0.006; relative risk=3.590).


CONCLUSIONS
The eNOS -786C allele is an independent risk factor for readmission due to a recurrent attack of coronary spasm in patients with coronary spasm, even if the patients have taken calcium channel blockers and/or nitrate.
Nishijima
Tsunenori
T
The Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Nakayama
Masafumi
M
Yoshimura
Michihiro
M
Abe
Koji
K
Yamamuro
Megumi
M
Suzuki
Satoru
S
Shono
Makoto
M
Sugiyama
Seigo
S
Saito
Yoshihiko
Y
Miyamoto
Yoshihiro
Y
Nakao
Kazuwa
K
Yasue
Hirofumi
H
Ogawa
Hisao
H
D000328:Adult; D000368:Aged; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use; D002423:Cause of Death; D003324:Coronary Artery Disease / Q000201:enzymology / Q000235:genetics; D003329:Coronary Vasospasm / Q000201:enzymology* / Q000235:genetics*; D003596:Cytosine; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D010359:Patient Readmission; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors; D013941:Thymine
D002121:Calcium Channel Blockers; D003596:Cytosine; D052250:Nitric Oxide Synthase Type III; D013941:Thymine