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

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 (242C-->T in the NADH/NADPH oxidase p22 phox gene) in men and two polymorphisms (-1171/5A-->6A in the stromelysin-1 gene and -634C-->G 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.