Common genetic variation of β1- and β2-adrenergic receptor and response to four classes of antihypertensive treatment

Abstract

Varying results have been reported on the association of beta-adrenergic receptor polymorphisms with blood pressure (BP) response to beta-blockers. We investigated the influence of ADRB1 Ser49Gly and Arg389Gly, and ADRB2 Gly16Arg and Glu27Gln polymorphisms on ambulatory BP response to bisoprolol and three other antihypertensive drug monotherapies in a placebo-controlled, double-blind, cross-over study with 233 moderately hypertensive men. ADRB1 Ser49Ser homozygotes tended to have a better ambulatory BP response to bisoprolol but the difference was statistically nonsignificant. ADRB1 Arg389Arg homozygotes did not show better BP response to bisoprolol than the other genotypes. There were no significant associations of ADRB2 polymorphisms with BP responses to any of the study drugs. The results from this controlled study in hypertensive men do not support clinical use of common polymorphisms in ADRB1 and ADRB2 in predicting BP responses to beta-blockers or to three other antihypertensive drugs.

A Physiologic Approach to the Pharmacogenomics of Hypertension

“…However, negative studies, including larger, well-powered investigations, predominate suggesting that rs1801253 cannot reliably predict antihypertensive response, rate control, or heart failure outcomes 11,17,[53][54][55][56][57][58] .…”

Stroke Pharmacogenetics

“…Studies examining the effect of common polymorphisms in the b (beta)1-adrenergic receptor (ADRB1) on blood pressure have been con fl icting. For those carrying the ADRB1 Ser49Ser homozygote genotype, BP response to bisoprolol was better than in the Ser49Gly heterozygotes (1.6 and 1.4 mmHg differences in systolic and diastolic BP response, p = 0.04 and 0.06, respectively) [ 181 ] . Similar results were seen in the ADRB1 Gly389Gly homozygotes, in whom BP response was superior than in those with the Arg389Arg homozygote genotype.…”

Genetic discoveries in hypertension: steps on the road to therapeutic translation

“…Candidate genes have been sourced from biological pathways known to be involved in blood pressure control, namely, components of the RAAS,45 natriuretic peptides,46 β-adrenergic receptors,47 and renal sodium retention 48. Not all studies show significant associations between genetic variants and response to antihypertensive medications.…”