Skip to main content
. Author manuscript; available in PMC: 2011 Mar 4.
Published in final edited form as: Curr Opin Mol Ther. 2010 Jun;12(3):294–304.

Table 2.

Summary of variants with pharmacogenetic interactions for β-blocker therapy in heart failure.

Gene Polymorphism/mutation rs number Molecular phenotype Clinical phenotype Reference
ADRB1 Arg389Gly rs1801253 Arg389 demonstrated differential effects on adenylyl levels in normal and heart failure tissues. Increased survival or LVEF β-blocker response with Arg389Arg. Gly389 associated with greater survival response in a separate study. Possibly involved in gene-gene interactions. [44,47,51,56,57,92–94]
Ser49Gly rs1801252 Gly49 allele leads to greater receptor downregulation on stimulation. Lower 5-year mortality in Gly49 carriers on low-dose β-blockers, but no difference with high-doses. [95,96]
ADRB2 Glu27Gln rs1042714 Glu27 allele has decreased receptor downregulation. Glu27 allele associated with better response to carvedilol. [43,97]
Gly16Arg rs1042713 Gly16 allele has greater receptor downregulation with receptor stimulation. Increased risk of death or transplantation detected for Arg16/Gln27 double homozygotes. [45,97]
ADRA2C Exon 1 I/D rs61767072 D-allele results in loss of autoinhibition. Arg389 homozygotes carrying D-allele exhibited greatest LVEF improvements on β-blocker therapy. In bucindolol-treated patients, only WT-homozygotes exhibited reductions in mortality and transplantation. [53,57,98,99]
ACE Intron 16 I/D rs4646994 Increased ACE level associated with D-allele. D-allele associated with risk of death or transplantation in patients not receiving β-blockers. [56,83]
EDN1 rs5370
rs2071942		 rs5370
rs2071942		 SNPs of unknown functionality in tight LD. Study of placebo- and bucindolol- treated patients (n = 159 and 150, respectively) demonstrated significant interaction between treatment and genotype at both loci. [59]
GRK5 Gln41Leu rs17098707 Leu41 enhances β-adrenoreceptor desensitization. Leu41 leads to increased survival in African American patients in the absence of β-blockers. [47,55]

ACE angiotensin 1-converting enzyme, ADRA2C adrenergic receptor α 2c, ADRB1 adrenergic receptor β 1, ADRB2 adrenergic receptor β 2, EDN1 endothelin 1, GRK5 G-protein coupled receptor kinase 5, I/D insertion/deletion, LVEF left ventricular ejection fraction, WT wild-type