Association between beta-1 and beta-2 adrenergic receptor gene polymorphisms and the response to beta-blockade in patients with stable congestive heart failure

Pharmacogenet Genomics. 2005 Mar;15(3):137-42. doi: 10.1097/01213011-200503000-00001.

Abstract

Previous studies have clearly demonstrated the beneficial effect of beta-blockers in patients with stable congestive heart failure (CHF). beta-blockers improve left ventricular ejection fraction (LVEF) and reduce cardiac mortality. However, there is an interindividual variability in the response to these agents. Two studies have suggested a possible impact of some functional betaAR gene polymorphisms on the effects of beta-blockade. The objective of the study is to analyse the association between genetic variations in the beta1 or the beta2 adrenoreceptor (AR) gene and the effects of beta-blockade in patients with stable CHF. We studied 199 consecutive patients with stable CHF not treated with beta-blockers. Before introduction of beta-blockers and 3 months after the maximal tolerated dose was reached, patients underwent an echocardiography and a radionuclide angiography. The beta1ARGly389Arg, beta1ARSer49Gly, beta2ARGly16Arg, beta2ARGln27Glu and beta2ARThr164Ile polymorphisms were determined: beta-blockade resulted in a significant decrease in heart rate, a significant increase in LVEF (from 30+/-10% to 40+/-13%, P<0.0001). There was no association between the five polymorphisms and heart rate or LVEF, either before or after beta-blockade. Heart rate and LVEF responses to beta-blockade were not associated with the beta1AR or the beta2AR polymorphisms. betaAR polymorphisms did not explain the interindividual variability in the response to beta-blockers.

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use*
  • Aged
  • Alleles
  • Angiography
  • Bisoprolol / pharmacology
  • Carbazoles / pharmacology
  • Carvedilol
  • Codon
  • Down-Regulation
  • Echocardiography
  • Female
  • Gene Frequency
  • Heart Failure / drug therapy*
  • Heart Failure / genetics*
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Polymorphism, Genetic*
  • Propanolamines / pharmacology
  • Prospective Studies
  • Receptors, Adrenergic, beta-1 / genetics*
  • Time Factors
  • Treatment Outcome
  • Ventricular Function, Left / drug effects*

Substances

  • Adrenergic beta-Antagonists
  • Carbazoles
  • Codon
  • Propanolamines
  • Receptors, Adrenergic, beta-1
  • Carvedilol
  • Bisoprolol