A common beta1-adrenergic receptor polymorphism (Arg389Gly) affects blood pressure response to beta-blockade

Clin Pharmacol Ther. 2003 Apr;73(4):366-71. doi: 10.1016/s0009-9236(02)17734-4.

Abstract

Background: A common polymorphism of the beta(1)-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 beta-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 beta-adrenergic receptor antagonist, and this polymorphism may be an important determinant of variability in response to beta-blockade.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology*
  • Adult
  • Alleles
  • Atenolol / pharmacology*
  • Female
  • Genotype
  • Hemodynamics / drug effects*
  • Humans
  • Male
  • Pharmacogenetics
  • Polymorphism, Genetic
  • Receptors, Adrenergic, beta* / drug effects
  • Receptors, Adrenergic, beta* / genetics

Substances

  • Adrenergic beta-Antagonists
  • Receptors, Adrenergic, beta
  • Atenolol