The Glu298Asp polymorphism in the endothelial nitric oxide synthase gene is strongly associated with coronary spasm.
BACKGROUND
Coronary spasm seems to be associated with coronary nitric oxide deficiency.


OBJECTIVE
We investigated whether the Glu298Asp polymorphism in the endothelial nitric oxide synthase (eNOS) gene is a definite risk factor for coronary spasm and whether diffuse spasm involving normal-looking coronary artery correlates significantly with the Glu298Asp polymorphism, in contrast with focal spasm superimposed on an atherosclerotic plaque.


METHODS
A polymerase chain reaction followed by restriction fragment length polymorphism analysis was performed in 118 control participants and in 102 patients with variant angina and a similar degree of atherosclerotic burden. Patients with coronary spasm were divided into diffuse spasm and focal spasm subgroups according to morphological criteria.


RESULTS
There was a significantly higher incidence of the Glu298Asp polymorphism in the coronary spasm group than in the control group (21.5% compared with 8.5%, P=0.006). Multiple logistic regression analysis using risk factors and the Glu298Asp polymorphism showed that the most important predictive factor for coronary spasm was the Glu298Asp polymorphism (odds ratio 2.83, 95% confidence interval 1.25-6.41, P=0.009). The diffuse spasm subgroup had a significantly higher frequency of the Glu298Asp polymorphism than the control group (25.9% compared with 8.5%, P=0.002). However, the focal spasm subgroup did not differ from the control group in the frequency of Glu298Asp polymorphism.


CONCLUSIONS
The Glu298Asp polymorphism in the eNOS gene is a definite risk factor for coronary spasm, especially for diffuse coronary spasm. This result supports the notion that diffuse coronary spasm is significantly associated with endothelial dysfunction, in contrast to focal spasm.
Chang
Kiyuk
K
Department of Internal Medicine, Catholic University of Korea, Seoul, South Korea.
Baek
Sang Hong
SH
Seung
Ki-Bae
KB
Kim
Pum-Joon
PJ
Ihm
Sang-Hyun
SH
Chae
Jang-Seong
JS
Kim
Jae-Hyung
JH
Hong
Soon-Jo
SJ
Choi
Kyu-Bo
KB
D003329:Coronary Vasospasm / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
D005819:Genetic Markers; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III