Klotho gene polymorphism may be a genetic risk factor for atherosclerotic coronary artery disease but not for vasospastic angina in Japanese

Background: The klotho gene, originally identified by insertional mutagenesis in mice, suppresses multiple aging phenotypes, including atherosclerosis. We tested the hypothesis that the G-395A polymorphism of the klotho gene is associated with increased risk for 2 types of ischemic heart disease in Japanese. Methods: The study population consisted of 197 patients with coronary heart disease (CAD) who had > 75% luminal diameter narrowing, 77 patients with vasospastic angina (VSA) without significant fixed coronary artery disease, and 331 healthy control subjects. Results: The frequency of the A allele carriers of the klotho gene was significantly higher in the CAD group than in the control group (29.9% vs. 19.0%). The unadjusted odds ratio for CAD in the A allele carriers compared with the control group was 1.82 (p=0.004) and a traditional risk-adjusted logistic regression model revealed that the A allele was an independent predictor of CAD (odds ratio, 1.76; p=0.03). In contrast, the frequency of the A allele carriers was not significantly different in the VSA group (23.4%; adjusted odds ratio, 1.18. Conclusions: The -395A polymorphism of the human klotho gene may be a genetic risk factor for IHD and not for VSA. (c) 2006 Elsevier B.V. All rights reserved.