Beta-adrenergic receptor gene polymorphisms and hemodynamic response to dobutamine during dobutamine stress echocardiography

Pharmacogenomics J. 2008 Dec;8(6):408-15. doi: 10.1038/sj.tpj.6500490. Epub 2008 Feb 5.

Abstract

Our objective was to determine if beta(1)-adrenergic receptor (beta(1)-AR) and beta(2)-AR gene polymorphisms influence heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) response to dobutamine during dobutamine stress echocardiography (DSE). Patients (n=163) undergoing clinically indicated DSE were enrolled. Dobutamine doses were titrated from 5 to 40 microg kg(-1) min(-1) at 3 min intervals and HR, SBP and DBP were measured. Genotypes were determined for beta(1)-AR Ser49Gly, beta(1)-AR Arg389Gly, beta(2)-AR Arg16Gly and beta(2)-AR Gln27Glu polymorphisms by polymerase chain reaction-restriction fragment length polymorphism analysis, pyrosequencing and single primer extension methods. beta(2)-AR Glu27 homozygotes had a greater HR response at the highest dobutamine dose than Gln27 carriers (P=0.002). Beta(2)-AR Gly16 homozygotes had a lower HR response during 5-30 microg kg(-1) min(-1) of the dobutamine infusion protocol compared to Arg16 carriers (P=0.03). Differences in SBP by beta(2)-AR codon 16 genotype and DBP by beta(1)-AR codon 389 genotype were found at baseline and were maintained throughout DSE (P=0.06 and 0.02, respectively). However, the magnitude of SBP and DBP response to dobutamine did not differ significantly by beta(2)-AR codon 16 or beta(1)-AR codon 389 genotypes, respectively. These data suggest that the four selected beta(1)- and beta(2)-AR polymorphisms do not substantially influence the magnitude of hemodynamic response to dobutamine during DSE.

Publication types

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

MeSH terms

  • Aged
  • Blood Pressure / drug effects*
  • Cohort Studies
  • Dobutamine / administration & dosage*
  • Dobutamine / pharmacology
  • Echocardiography / methods*
  • Female
  • Genotype
  • Heart Rate / drug effects*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Receptors, Adrenergic, beta / genetics*

Substances

  • Receptors, Adrenergic, beta
  • Dobutamine