Association of common polymorphisms in β1-adrenergic receptor with antihypertensive response to carvedilol.

Abstract

Marked interpatient variability exists in the blood pressure response to carvedilol, a nonselective β-blocker. Here we evaluated the influence of 4 common polymorphisms in genes of the β-adrenergic receptor on the antihypertensive efficacy of carvedilol in patients in a double-blinded monotherapy study. Eighty-seven subjects with uncomplicated essential hypertensive (49% men; age = 52.2 ± 11.1 years) from Jilin province of China were enrolled in the study, and 5 of them discontinued the treatment due to adverse effects. Both systolic and diastolic blood pressures (DBPs) were measured before and after 7 days of treatment with carvedilol (10 mg/d). Genotypes of the β1-adrenergic receptor (ADRB1 Ser49Gly and Arg389Gly) and β2-adrenergic receptor (ADRB2 Gly16Arg and Glu27Gln) were determined by polymerase chain reaction with restriction fragment length polymorphism. Patients homozygous for ADRB1 Arg389 had an approximately 4-fold greater reduction in DBPs than those homozygous for ADRB1 Gly389 (10.61 vs. 2.62 mm Hg, P = 0.013). The ADRB1 haplotype was also a significant predictor of response, as patients with the Gly49Arg389/Ser49Arg389 haplotype pair had a 5.7-fold greater reduction in DBPs than those homozygous for the Ser49Gly389 haplotype (16.11 vs. 2.83 mm Hg, P = 0.0055). An association was not found between ADRB2 polymorphism and carvedilol responsiveness in antihypertensive therapy. This study provides the first evidence to support that ADRB1 polymorphisms play an important role in the DBPs response to carvedilol treatment in patients with essential hypertension.