title: G protein-coupled receptor kinase 5 gene polymorphisms are associated with postoperative atrial fibrillation after coronary artery bypass grafting in patients receiving β-blockers.
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).
  
  
  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.
authors.affiliation: Department of Anesthesiology, Duke Perioperative Genomics Program, Duke University Medical Center, Durham, NC.
authors.forename: Miklos D
authors.initials: MD
authors.lastname: Kertai
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC.
authors.forename: Yen-Wei
authors.initials: YW
authors.lastname: Li
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC.|Molecular Physiology Institute, Duke University Medical Center, Durham, NC.
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Molecular Physiology Institute, Duke University Medical Center, Durham, NC.|Department of Medicine, Division of Cardiology, Duke University Medical Center, Durham, NC.
authors.forename: Svati H
authors.initials: SH
authors.lastname: Shah
authors.affiliation: Molecular Physiology Institute, Duke University Medical Center, Durham, NC.|Department of Medicine, Division of Cardiology, Duke University Medical Center, Durham, NC.
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
authors.affiliation: Department of Anesthesiology, Duke Perioperative Genomics Program, Duke University Medical Center, Durham, NC.
authors.forename: Manuel L
authors.initials: ML
authors.lastname: Fontes
authors.affiliation: Department of Anesthesiology, Duke Perioperative Genomics Program, Duke University Medical Center, Durham, NC.
authors.forename: Mark
authors.initials: M
authors.lastname: Stafford-Smith
authors.affiliation: Department of Anesthesiology, Duke Perioperative Genomics Program, Duke University Medical Center, Durham, NC.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Newman
authors.affiliation: Department of Anesthesiology, Duke Perioperative Genomics Program, Duke University Medical Center, Durham, NC.
authors.forename: Mihai V
authors.initials: MV
authors.lastname: Podgoreanu
authors.affiliation: Department of Anesthesiology, Duke Perioperative Genomics Program, Duke University Medical Center, Durham, NC.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Mathew
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000368:Aged; D001281:Atrial Fibrillation / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D001026:Coronary Artery Bypass; D005260:Female; D054774:G-Protein-Coupled Receptor Kinase 5 / Q000235:genetics*; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications; D015398:Signal Transduction
chemical_list: D000319:Adrenergic beta-Antagonists; D054774:G-Protein-Coupled Receptor Kinase 5; C517898:GRK5 protein, human
keywords: atrial fibrillation; coronary artery bypass; polymorphism, single nucleotide