Frequency of genetic polymorphism for adrenergic receptor beta and cytochrome p450 2D6 enzyme, and effects on tolerability of beta-blocker therapy in heart failure with reduced ejection fraction patients: The Beta GenTURK study

Turk Kardiyol Dern Ars. 2016 Sep;44(6):457-65. doi: 10.5543/tkda.2016.10733.

Abstract

Objective: The present objective was to determine frequency of Arginine389Glycine (Arg389Gly) and Cytochrome p450 2D6*10 (Cyp2D6*10) polymorphism in cases of heart failure-reduced ejection fraction (HFREF), and to evaluate the influence of the polymorphisms in response to beta-blocker (BB) therapy.

Methods: A total of 206 HFREF patients and 90 healthy controls were prospectively enrolled. Genotypes for Arg389Gly and Cyp2D6*10 polymorphisms of the healthy controls and 162 of the 206 heart failure (HF) patients were measured, identified by polymerase-chain-reaction- and restriction-fragment-length-polymorphism analysis. HFREF patients and healthy controls were compared regarding Arg389Gly polymorphism. The HFREF patients were separated into 2 subgroups based on achievement of maximal target dose (MTD) of BB.

Results: When comparing frequency of genotype distribution for Arg389Gly polymorphism in HFREF patients to the healthy controls, a statistically significant association was observed with CC genotype and Glisin-Glisin (GG) genotype (p<0.001, odds ratio [OR]=16, confidence interval [CI]: 3.8-67.9 and p<0.001, OR=0.3, CI: 0.2-0.6). Frequency of genotypes for Arg389Gly and Cyp2D6*10 polymorphism were similar in patients who could or could not achieve BB MTD (p=0.13 and p=0.60, respectively).

Conclusion: The frequency of Arg389Gly polymorphism in patients with HFREF in the present Turkish population differed from that of the healthy controls. However, neither Arg389Gly polymorphism nor Cyp2D6*10 polymorphism was associated with dose tolerability of BB therapy.

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use*
  • Aged
  • Cytochrome P-450 CYP2D6 / genetics*
  • Female
  • Gene Frequency / genetics*
  • Heart Failure* / drug therapy
  • Heart Failure* / epidemiology
  • Heart Failure* / genetics
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics*
  • Prospective Studies
  • Receptors, Adrenergic, beta-1 / genetics*
  • Stroke Volume
  • Turkey / epidemiology

Substances

  • ADRB1 protein, human
  • Adrenergic beta-Antagonists
  • Receptors, Adrenergic, beta-1
  • Cytochrome P-450 CYP2D6