Beta1- and alpha2c-adrenoreceptor variants as predictors of clinical aspects of dilated cardiomyopathy in people of African ancestry

Cardiovasc J Afr. 2008 Jul-Aug;19(4):188-93.

Abstract

Background: Although the beta1-adrenoreceptor (AR) Gly389Arg and alpha2c-AR Del322-325 gene variants are associated with the response to beta-AR-blocker therapy, whether this effect is associated with the risk for heart failure, or the severity or progression of heart failure is uncertain.

Aims: To assess the relationship between Gly389Arg and Del322-325 variants and the presence, severity and progression of idiopathic dilated cardiomyopathy (IDC) in 403 black South African patients.

Methods: Genotypes were identified using a restriction fragment length polymorphism-based technique and automated sequencing. Left ventricular ejection fraction (LVEF) and dimensions were determined at baseline and in 132 patients after six months of standard medical therapy excluding beta-AR-blockers (not indicated as standard care at the time of completing this study).

Results: All patients and controls genotyped for the alpha2c-AR variant were homozygous for the Del322-325 (risk) allele. The Gly389Arg polymorphism was not associated with IDC (control n = 429) (Arg389 allele homozygosity: odds ratio = 1.03, confidence limits = 0.78-1.35), nor did it predict LVEF and cavity dimensions either before or after therapy.

Conclusion: In patients homozygous for the risk allele of the alpha2c-AR variant, the beta1-AR variant neither increased the risk for IDC nor predicted its severity or progression in patients not receiving beta-AR-blockers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Black People / genetics*
  • Cardiomyopathy, Dilated / drug therapy
  • Cardiomyopathy, Dilated / ethnology
  • Cardiomyopathy, Dilated / genetics*
  • Cardiomyopathy, Dilated / pathology
  • Cardiomyopathy, Dilated / physiopathology
  • Cardiovascular Agents / therapeutic use
  • Case-Control Studies
  • Disease Progression
  • Drug Therapy, Combination
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Homozygote
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Prospective Studies
  • Receptors, Adrenergic, alpha-2 / genetics*
  • Receptors, Adrenergic, beta-1 / genetics*
  • Risk Factors
  • Severity of Illness Index
  • South Africa
  • Stroke Volume / drug effects
  • Stroke Volume / genetics
  • Treatment Outcome
  • Ventricular Function, Left / drug effects
  • Ventricular Function, Left / genetics

Substances

  • ADRA2C protein, human
  • Cardiovascular Agents
  • Receptors, Adrenergic, alpha-2
  • Receptors, Adrenergic, beta-1