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(Hypertension. 2001;37:286.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Association Analysis of ß₂-Adrenergic Receptor Polymorphisms With Hypertension in Japanese

Norihiro Kato; Takao Sugiyama; Hiroyuki Morita; Hiroki Kurihara; Tomohide Sato; Yukio Yamori; Yoshio Yazaki

From the Department of Internal Medicine, Teikyo (Japan) University School of Medicine (N.K., T. Sato); The Institute for Adult Diseases Asahi Life Foundation, Tokyo, Japan (T. Sugiyama); the Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo (Japan) (H.M., H.K); the Graduate School of Human and Environmental Studies, Kyoto (Japan) University (Y. Yamori); and The Hospital International Medical Center of Japan, Tokyo (Y. Yazaki).

Correspondence to Norihiro Kato, MD, PhD, Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan. E-mail nkato{at}med.teikyo-u ac.jp

Significant evidence has been provided for the pathophysiological involvement of the ß₂-adrenergic receptor (ADRB2) in hypertension. Among ADRB2 polymorphisms identified to date, 2 amino acid substitutions, Arg16Gly and Gln27Glu, and a promoter variant, T-47C, are considered functionally important. In particular, Arg16Gly was shown to be associated with hypertension in black and white subjects. To investigate the relevance of ADRB2 polymorphisms to hypertension, we undertook an extensive association study in a Japanese population. An association was tested in 2 ways. First, a case-control study was conducted in 842 hypertensive and 633 normotensive subjects. In addition to the overall comparison between case and control groups, each was stratified by body mass index and compared with an independent panel of 525 diabetic subjects. Second, ANOVA and multivariate analyses were performed to test the significance of an association between ADRB2 genotype and the level of blood pressure within the entire population except for 395 subjects who had been under treatment for hypertension. Although no significant association was observed for Arg16Gly and T-47C, 2 analytical methods indicated a marginal association (P=0.01 to 0.04) between the Glu27 variant and lower blood pressure levels. Given such a normotensive propensity, the odds ratio for Glu27 versus Gln27 allele frequencies was estimated to be 0.74, with a wide confidence interval (95% CI, 0.55 to 0.99) reflecting the low Glu27-allele frequency (6% to 8%) in Japanese. There were no apparent confounding influences of obesity and diabetes on the postulated association. Our data suggest that 3 ADRB2 polymorphisms tested are unlikely to confer principal genetic susceptibility for hypertension in the Japanese population. However, further investigation is warranted to clarify the relevance of ADRB2 polymorphisms to blood pressure regulation.

Key Words: hypertension, essential • receptors, adrenergic • obesity • genetics

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