BACKGROUND AND OBJECTIVES: Oxidative stress plays an important role in the pathogenesis of coronary atherosclerosis and spasm. We investigated whether the polymorphisms in two oxidative stress-related genes, paraoxonase and p22phox, are associated with risks of coronary artery spasm and stenosis. SUBJECTS AND METHODS: The study comprised of 116 patients with variant angina, 118 patients with coronary artery stenosis and 117 control subjects, who were all classified by coronary angiography. In all three groups, the genotype frequencies of the Q192R polymorphism of the paraoxonase gene and C242T polymorphism of the p22phox gene were analyzed, and the serum thiobarbituric acid-reactive substance concentrations measured. RESULTS: The frequency of the RR genotype of the paraoxonase Q192R polymorphism was significantly higher in patients with variant angina and coronary artery stenosis than in the control subjects (40.4% in variant angina and 37.8% in coronary artery stenosis vs. 24.7% in control, p=0.020 and 0.048, respectively). From the multivariate analysis, the odds ratio of the RR genotype was 2.240 for variant angina (95% confidence interval ; 1.012-4.956), and 2.333 for coronary artery stenosis (95% confidence interval ; 1.140-4.777), in relation to the control subjects. The thiobarbituric acid-reactive substance level was significantly higher in the RR type than in the QQ+QR types (RR vs. QQ+QR : 1.106+/-0.420 nmol/mL vs. 0.949+/-0.311 nmol/mL, p=0.028). There was no significant difference in the prevalence of the C242T polymorphism of the p22phox gene between the three groups. CONCLUSION: The RR genotype of the paraoxonase gene Q192R polymorphism was found to be an independent risk factor for both coronary spasm and stenosis.