Genetic polymorphisms in ADRB2 and ADRB1 are associated with differential survival in heart failure patients taking β-blockers

Pharmacogenomics J. 2022 Feb;22(1):62-68. doi: 10.1038/s41397-021-00257-1. Epub 2021 Oct 12.


Single nucleotide polymorphisms (SNPs) have been associated with differential beta-blocker (BB) effects on heart rate, blood pressure, and left ventricular ejection fraction in various patient populations. This study aimed to determine if SNPs previously associated with BB response are also associated with differential survival in heart failure (HF) patients receiving BBs. HF patient data were derived from electronic health records and the Social Security Death Index. Associations and interactions between BB dose, SNP genotype, and the outcome of death were assessed using a Cox proportional-hazard model adjusting for covariates known to be associated with differential survival in HF patients. Two SNPs, ADRB1 Arg389Gly and ADRB2 Glu27Gln, displayed significant interactions (Pint = 0.043 and Pint = 0.017, respectively) with BB dose and their association with mortality. Our study suggests that ADRB2 27Glu and ADRB1 389Arg may confer a larger survival benefit with higher BB doses in patients with HF.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage
  • Adrenergic beta-Antagonists / therapeutic use*
  • Aged
  • Aged, 80 and over
  • Dose-Response Relationship, Drug
  • Female
  • Genotype
  • Heart Failure / drug therapy*
  • Heart Failure / mortality*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics
  • Polymorphism, Single Nucleotide
  • Proportional Hazards Models
  • Receptors, Adrenergic, beta-1 / genetics*
  • Receptors, Adrenergic, beta-2 / genetics*
  • Survival Analysis


  • ADRB1 protein, human
  • ADRB2 protein, human
  • Adrenergic beta-Antagonists
  • Receptors, Adrenergic, beta-1
  • Receptors, Adrenergic, beta-2