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European Heart Journal 2004 25(11):970-977; doi:10.1016/j.ehj.2004.02.020
Copyright © 2004 by the European Society of Cardiology.
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Clinical research

Genetic risk and gene–environment interaction in coronary artery spasm in Japanese men and women

Yosuke Murasea,b, Yoshiji Yamadad,*, Akihiro Hirashikia, Sahoko Ichiharab,d, Hirofumi Kandaa, Masato Wataraie, Fumimaro Takatsue, Toyoaki Muroharab and Mitsuhiro Yokotac

a Division of Cardiology, Okazaki City Hospital, Okazaki, Japan
b Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
c Department of Clinical Pathophysiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
d Department of Human Functional Genomics, Life Science Research Centre, Mie University, 1515 Kamihama, Tsu, Mie 514-8507, Japan
e Division of Cardiology, Kosei Hospital, Anjo, Japan

* Corresponding author. Tel.: +81-59-231-5387; fax: +81-59-231-5388
E-mail address: yamada{at}gene.mie-u.ac.jp

Received 28 October 2003; revised 16 February 2004; accepted 19 February 2004 See page 900 for the editorial comment on this article1

Abstract

Aims The aim of the study was to identify genes that confer susceptibility to coronary artery spasm and clarify the interaction between genetic and environmental factors in this condition.

Methods and results The study population comprised 2188 Japanese individuals, including 593 subjects with coronary artery spasm (453 men, 140 women) and 1595 controls (762 men, 833 women). The genotypes for 35 polymorphisms of 29 candidate genes were determined with an allele-specific DNA primer–probe assay. Multivariable logistic regression analysis adjusted for age, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, hypercholesterolaemia, and hyperuricaemia revealed a significant association with coronary artery spasm of one polymorphism (242CT in the NADH/NADPH oxidase p22 phox gene) in men and two polymorphisms (–1171/5A6A in the stromelysin-1 gene and –634CG in the interleukin-6 gene) in women. A stepwise forward selection procedure revealed that smoking was the most important risk factor for coronary artery spasm and that the effects of these polymorphisms on this condition were statistically independent of smoking.

Conclusion The NADH/NADPH oxidase p22 phox gene is a susceptibility locus for coronary artery spasm in men, and the stromelysin-1 and interleukin-6 genes are susceptibility loci in women.

Key Words: Coronary artery spasm • Vasospastic angina • Myocardial infarction • Genetics • Polymorphism • Coronary risk factor


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