Role of Beta-Adrenergic Receptor Gene Polymorphisms in the Long-Term Effects of Beta-Blockade with Carvedilol in Patients with Chronic Heart Failure

Abstract

Beta1-AR Arg389Gly and beta2-AR Arg16Gly SNPs are not related to the response to carvedilol therapy. In contrast, the Gln27Glu SNP is a determinant of the LVEF response to this agent in patients with chronic HF.

Beta2-adrenergic receptor genotype influences the effect of nonselective vs. selective beta-blockade on baroreflex function in chronic heart failure

“…Together with previous data on a beneficial response to carvedilol in CHF patients homozygous for the Glu27 allele [10,17] our findings suggest that nonselective βAR-blocker treatment efficacy interacts with β 2 AR genotype. This pharmacogenetic interaction may contribute to the improved outcomes with either carvedilol [22] or the Gly16/Glu27 β 2 AR haplotype [13,25] in cardiovascular disease.…”

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] .…”

“…Variants of ADRB2 have been associated with asthma exacerbations and salmeterol response 59,60 . However, antihypertensive and cardiac investigations of beta-blockers and ACEIs have yielded mixed results of the ADRB2 variants, rs1042713 and rs1042714, in predicting BP and congestive heart failure responses 10,17,56,57,[61][62][63] . Rs4994, a polymorphism in ADRB3, has been evaluated in hypertensive studies.…”

Polymorphisms of the Beta Adrenergic Receptor Predict Left Ventricular Remodeling Following Acute Myocardial Infarction

“…Pharmacogenetic studies may also help to identify which patients may benefit from combined chronic β1 and β2 receptor blockade as opposed to β1 receptor blockade alone. A recent study indeed did show a greater response to carvedilol a non-selective beta-blocker, in patients with the Glu27Glu genotype and chronic heart failure [35]. In the future pharmacogenetic studies of the β-AR may therefore guide the clinician toward improved individual risk stratification and personalized beta-blocker therapy.…”