A common β1-adrencrgic receptor polymorphism (Arg389Gly) affects blood pressure response to β-blockade

G. G. Sofowora, V. Dishy, M. Muszkat, H. G. Xie, R. B. Kim, P. A. Harris, H. C. Prasad, D. W. Byrne, U. B. Nair, Alastair J.J. Wood*, C. M. Stein

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

159 Scopus citations

Abstract

Background: A common polymorphism of the β1-adrenergic receptor Arg389Gly markedly affects function in vitro, but little is known about its in vivo significance. Methods and Results: Resting and exercise hemodynamic responses were measured in subjects homozygous for Arg389 (n = 21) or Gly389 (n = 13) alleles before and 3 hours after administration of a β-blocker, atenolol. Demographic characteristics and atenolol concentrations were similar in the two genotypic groups. Genotype had a marked effect on resting hemodynamic responses to atenolol, with Arg389-homozygous subjects having a larger decrease in resting systolic blood pressure (8.7 ± 1.3 mm Hg versus 0.2 ± 1.7 mm Hg, P < .001) and mean arterial blood pressure (7.2 ± 1.0 mm Hg versus 2.0 ± 1.7 mm Hg, P = .009). Attenuation of exercise-induced hemodynamic responses by atenolol was not affected by genotype. Conclusions: There is reduced sensitivity of Gly389 homozygotes to a β-adrenergic receptor antagonist, and this polymorphism may be an important determinant of variability in response to β-blockade.

Original languageAmerican English
Pages (from-to)366-371
Number of pages6
JournalClinical Pharmacology and Therapeutics
Volume73
Issue number4
DOIs
StatePublished - 1 Apr 2003
Externally publishedYes

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