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Arg389Gly β1-adrenoceptor polymorphism varies in frequency among different ethnic groups but does not alter response in vivo

Xie, Hong-Guanga; Dishy, Victora; Sofowora, Gbengaa; Kim, Richard B.a; Landau, Ruthb; Smiley, Richard M.b; Zhou, Hong-Haoc; Wood, Alastair J. J.a; Harris, Pauld; Stein, C. Michaela

Original Article

There are marked interethnic differences in β1-adrenoceptor-mediated responsiveness, with sensitivity decreased in African-Americans and increased in Chinese compared with Caucasians. Therefore, the frequency of a common naturally occurring polymorphism of the human β1-adrenoceptor gene (Arg389Gly), which has functional importance in vitro, was determined in 194 African-Americans, 316 Caucasian-Americans, 221 Hispanic-Americans and 142 Chinese. African-Americans were found to have a significantly lower frequency of the Arg389 allele than the other three ethnic groups (all P< 0.01). In the populations studied, the order of the distribution of the Arg389 allele was: Chinese (74%) > Caucasians (72%) > Hispanics (67%) > African-Americans (58%). To determine the functional significance of the Arg389Gly β1-adrenoceptor polymorphism, in-vivo heart rate responses to exercise were compared in healthy subjects homozygous for the Arg (n = 9) and Gly (n = 8) alleles. Heart rate response to exercise was not affected by genotype (P = 0.4). Although ethnic differences in the frequency of the β1-adrenoceptor Arg389Gly polymorphism exist, the polymorphism does not appear to have functional significance in healthy subjects and therefore may not contribute to ethnic differences in response to drugs acting through the β1-adrenoceptor.

aDivision of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA, bDepartment of Anesthesiology, Columbia University Presbyterian Medical Center, New York, NY, USA, cBasic and Clinical Pharmacology Institute, Hunan Medical University, Changsha, Hunan, China and dGeneral Clinical Research Center and Department of Biomedical Engineering, Vanderbilt University School of Medicine, Nashville, TN, USA

Received 25 April 2000; accepted 25 September 2000

Correspondence to Dr C. Michael Stein, Vanderbilt University Medical Center, Division of Clinical Pharmacology, MRB-1, Room 560C, Nashville, TN 37232–6602, USA Tel: +1 615 343 8701; fax: +1 615 343 2551;

© 2001 Lippincott Williams & Wilkins, Inc.