• Circ Cardiovasc Genet · Oct 2014

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

    • Miklos D Kertai, Yen-Wei Li, Yi-Ju Li, Svati H Shah, William E Kraus, Manuel L Fontes, Mark Stafford-Smith, Mark F Newman, Mihai V Podgoreanu, Joseph P Mathew, and Duke Perioperative Genetics and Safety Outcomes (PEGASUS) Investigative Team.
    • From the Department of Anesthesiology, Duke Perioperative Genomics Program (M.D.K., M.L.F., M.S.-S., M.F.N., M.V.P., J.P.M.), Department of Biostatistics and Bioinformatics (Y.-W.L., Y.-J.L.), Molecular Physiology Institute (Y.-J.L., S.H.S., W.E.K.), and Department of Medicine, Division of Cardiology (S.H.S., W.E.K.), Duke University Medical Center, Durham, NC. miklos.kertai@duke.edu.
    • Circ Cardiovasc Genet. 2014 Oct 1;7(5):625-33.

    BackgroundWe 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 ResultsTwo 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)).ConclusionsIn patients undergoing coronary artery bypass grafting, genetic variation in GRK5 is associated with postoperative AF despite perioperative BB therapy.© 2014 American Heart Association, Inc.

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