G protein-coupled receptor kinase 5 gene polymorphisms are associated with postoperative atrial fibrillation after coronary artery bypass grafting in patients receiving β-blockers

Duke Perioperative Genetics and Safety Outcomes (PEGASUS) Investigative Team

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background: We hypothesized that genetic variations in the adrenergic signaling pathway and cytochrome P450 2D6 enzyme are associated with new-onset atrial fibrillation (AF) in patients who underwent coronary artery bypass grafting and were treated with perioperative β-blockers (BBs).Methods and Results-Two cohorts of patients who underwent coronary artery bypass grafting and received perioperative BBs at Duke University Medical Center were studied. In a discovery cohort of 563 individuals from the Perioperative Genetics and Safety Outcomes Study (PEGASUS), using a covariate-adjusted logistic regression analysis, we tested 492 single-nucleotide polymorphisms (SNPs) in 10 candidate genes of the adrenergic signaling pathway and cytochrome P450 2D6 for association with postoperative AF despite perioperative BB therapy. SNPs meeting a false discovery rate ≤0.20 (P<0.002) were then tested in the replication cohort of 245 individuals from the Catheterization Genetics biorepository. Of the 492 SNPs examined, 4 intronic SNPs of the G protein-coupled kinase 5 (GRK5) gene were significantly associated with postoperative AF despite perioperative BB therapy in the discovery cohort with additive odds ratios between 1.72 and 2.75 (P=4.78×10-5 to 0.0015). Three of these SNPs met nominal significance levels in the replication cohort with odds ratios between 2.07 and 2.60 (P=0.007 to 0.016). However, meta-analysis of the 2 data sets cohorts suggested strong association with postoperative AF despite perioperative BB therapy in all 4 SNPs (meta-P values from 1.66×10-6 to 3.39×10-5).Conclusions-In patients undergoing coronary artery bypass grafting, genetic variation in GRK5 is associated with postoperative AF despite perioperative BB therapy.

Original languageEnglish
Pages (from-to)625-633
Number of pages9
JournalCirculation: Cardiovascular Genetics
Volume7
Issue number5
DOIs
Publication statusPublished - Oct 1 2014

Keywords

  • Atrial fibrillation
  • Coronary artery bypass
  • Polymorphism
  • Single nucleotide

ASJC Scopus subject areas

  • Genetics
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

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