Effects of GRK5 and ADRB1 polymorphisms influence on systolic heart failure

J Transl Med. 2015 Feb 1:13:44. doi: 10.1186/s12967-015-0402-7.

Abstract

Background: G-protein receptor kinase 5 (GRK5) Gln41 > Leu and β1-adrenergic receptor (ADRB1) Arg389 > Gly polymorphisms presented the different distribution of genotype frequencies between Caucasian American and African American, and produced the difference in β-blocker treatment effect among them with systolic heart failure (SHF).

Objective: This study sought to identify the distributed characteristics of these variant genotypes in Chinese population, and influence of GRK5 and ADRB1 polymorphisms on SHF morbidity and β-blocker treatment effect in patients with SHF.

Methods: This study was based on cross-sectional survey data. 1794 and 1718 subjects' ADRB1 and GRK5 gene sequencing (sanger method) data were achieved respectively. Blood samples collection, clinical laboratory detection, electrocardiogram and echocardiography examinations were performed. Medication usage was confirmed at in-hospital visits or the questionnaire by personal interview.

Results: GRK5 Leu41Leu genotype was not found in our Chinese population. In non-SHF population, allele frequencies of GRK5 Gln41 and Leu41 were 2782 (0.992) and 22 (0.008) (Hardy-Weinberg equilibrium test χ(2) = 0.088, P = 0.767), and allele frequencies of ADRB1 Arg389 and Gly389 were 2127 (0.715) and 849 (0.285) (χ(2) = 0.272, P = 0.602). In SHF patients, allele frequencies of Gln41 and Leu41 were 446 (0.991) and 4 (0.009) (χ(2) = 0.018, P = 0.893), and allele frequencies of Arg389 and Gly389 were 331 (0.726) and 125 (0.274) (χ(2) = 1.892, P = 0.169). Further in logistic regression model, these ADRB1 and GRK5 variants were not significantly independently associated with the risk of SHF morbidity. Those carrying genotype ADRB1 Gly389Gly did not reduce significantly the risk of SHF morbidity after β-blocker therapy.

Conclusions: GRK5 Leu41Leu genotype was not found in our Chinese population, neither ADRB1 nor GRK5 variants presented independently associated with the risk of SHF morbidity, most ADRB1 and GRK5 polymorphisms did decrease significantly the risk of SHF morbidity after β-blocker therapy except for those carrying genotype ADRB1 Gly389Gly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use
  • Base Sequence
  • G-Protein-Coupled Receptor Kinase 5 / genetics*
  • Heart Failure, Systolic / drug therapy
  • Heart Failure, Systolic / genetics*
  • Humans
  • Models, Genetic
  • Molecular Sequence Data
  • Multivariate Analysis
  • Polymorphism, Single Nucleotide / genetics*
  • Receptors, Adrenergic, beta-1 / genetics*
  • Sequence Analysis, DNA

Substances

  • ADRB1 protein, human
  • Adrenergic beta-Antagonists
  • Receptors, Adrenergic, beta-1
  • G-Protein-Coupled Receptor Kinase 5
  • GRK5 protein, human