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

OBJECTIVES: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. METHODS: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. RESULTS: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. CONCLUSIONS: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.