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

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. Clinical Pharmacology & Therapeutics (2003) 73, 366–371; doi: 10.1016/S0009-9236(02)17734-4