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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1680.)
© 2002 American Heart Association, Inc.

Atherosclerosis

Heme Oxygenase-1 Gene Promoter Polymorphism Is Associated With Coronary Artery Disease in Japanese Patients With Coronary Risk Factors

Hideaki Kaneda; Minoru Ohno; Junichi Taguchi; Masako Togo; Hideki Hashimoto; Ken Ogasawara; Tadanori Aizawa; Nobukazu Ishizaka; Ryozo Nagai

From the Department of Cardiovascular Medicine (H.K., M.O., J.T., N.I., R.N.) and the Department of Metabolic Diseases (M.T.), The University of Tokyo, Graduate School of Medicine; the Department of Hygiene and Public Health (H.H.), Teikyo University School of Medicine; and the Cardiovascular Institute (K.O., T.A.), Tokyo, Japan.

Correspondence to Minoru Ohno, MD, Department of Cardiovascular Medicine, The University of Tokyo, Graduate School of Medicine, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail mino-tky{at}umin.ac.jp

Abstract

Objective— Heme oxygenase (HO) is important in the defense against oxidative stress and as a factor in an antiatherogenic mechanism. Compared with long (GT)_n repeats, short (GT)_n repeats in the human HO-1 gene promoter were shown to have higher transcriptional activity in response to oxidative stress. There is a strong link between oxidative stress and the pathogenesis of coronary artery disease (CAD).

Methods and Results— We screened the allelic frequencies of (GT)_n repeats in the HO-1 gene promoter in 577 patients who underwent coronary angiography. Because the distribution of numbers of (GT)_n repeats was bimodal, we divided the alleles into 2 subclasses: class S included shorter (<27) repeats, and class L included longer (27) repeats. Multivariate logistic regression models including standard coronary risk factors revealed that the genotypes were significantly related to CAD status in hypercholesterolemic, diabetic patients or in smokers. In this study, the patients with shorter GT repeats were less likely to have CAD.

Conclusions— Length polymorphism in the HO-1 gene promoter is related to CAD susceptibility in Japanese people who also have coronary risk factors such as hypercholesterolemia, diabetes, and smoking. HO-1 may play an antiatherogenic role in Japanese patients with these coronary risk factors.

Key Words: heme oxygenase • oxidative stress • coronary disease • polymorphism • risk factors

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