β1-Adrenergic Receptor Gene Polymorphisms and the Acute Response to Atenolol in Healthy Young Japanese Subjects

Abstract

Polymorphisms at codons 49 and 389 of the β1-adrenergic receptor gene have been shown to alter the receptor function in vitro, whereas it remains controversial whether they influence the response to β-blocker in vivo. In the present study, we investigated whether these polymorphisms influence the acute changes of heart rate and blood pressure induced by the β1-adrenergic receptor–selective blocker atenolol in healthy young Japanese. A double-blind study was conducted with 307 subjects randomly allocated 2:1 to atenolol (50 mg) or placebo groups. Heart rate and blood pressure were significantly reduced after administration of atenolol in comparison to the placebo. In 207 subjects allocated to the atenolol group, the numbers of Ser/Ser, Ser/Gly, and Gly/Gly allele carriers for codon 49 were 159, 46, and 2, respectively; and those of Arg/Arg, Arg/Gly, and Gly/Gly for codon 389 were 129, 66, and 12, respectively. No significant association was identified between the changes in heart rate or blood pressure and either of the two polymorphisms. There was also no difference in the changes in heart rate or blood pressure among the diplotypes. The results of the present study do not support clinical use of genotyping for these polymorphisms to predict responses to β-blockers. Keywords:: β1-adrenergic receptor, polymorphism, β-blocker, atenolol, randomized double-blind trial