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.
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.
Authors: Richard Fux; Klaus Mörike; Anne M T Pröhmer; Ursula Delabar; Matthias Schwab; Elke Schaeffeler; Gernot Lorenz; Christoph H Gleiter; Michel Eichelbaum; Kari T Kivistö Journal: Clin Pharmacol Ther Date: 2005-10 Impact factor: 6.875
Authors: Stephen B Liggett; Jeanne Mialet-Perez; Surai Thaneemit-Chen; Stewart A Weber; Scott M Greene; Danielle Hodne; Bradley Nelson; Jennifer Morrison; Michael J Domanski; Lynne E Wagoner; William T Abraham; Jeffrey L Anderson; John F Carlquist; Heidi J Krause-Steinrauf; Laura C Lazzeroni; J David Port; Philip W Lavori; Michael R Bristow Journal: Proc Natl Acad Sci U S A Date: 2006-07-14 Impact factor: 11.205
Authors: Julian Little; Julian P T Higgins; John P A Ioannidis; David Moher; France Gagnon; Erik von Elm; Muin J Khoury; Barbara Cohen; George Davey-Smith; Jeremy Grimshaw; Paul Scheet; Marta Gwinn; Robin E Williamson; Guang Yong Zou; Kim Hutchings; Candice Y Johnson; Valerie Tait; Miriam Wiens; Jean Golding; Cornelia van Duijn; John McLaughlin; Andrew Paterson; George Wells; Isabel Fortier; Matthew Freedman; Maja Zecevic; Richard King; Claire Infante-Rivard; Alex Stewart; Nick Birkett Journal: Hum Genet Date: 2009-02-01 Impact factor: 4.132
Authors: T Rau; H Wuttke; L M Michels; U Werner; K Bergmann; M Kreft; M F Fromm; T Eschenhagen Journal: Clin Pharmacol Ther Date: 2008-11-26 Impact factor: 6.875
Authors: William E Kraus; Christopher B Granger; Michael H Sketch; Mark P Donahue; Geoffrey S Ginsburg; Elizabeth R Hauser; Carol Haynes; L Kristin Newby; Melissa Hurdle; Z Elaine Dowdy; Svati H Shah Journal: J Cardiovasc Transl Res Date: 2015-08-14 Impact factor: 4.132
Authors: Miklos D Kertai; Wenjing Qi; Yi-Ju Li; Frederick W Lombard; Yutao Liu; Michael P Smith; Mark Stafford-Smith; Mark F Newman; Carmelo A Milano; Joseph P Mathew; Mihai V Podgoreanu Journal: J Mol Cell Cardiol Date: 2016-02-06 Impact factor: 5.000
Authors: Miklos D Kertai; Yunqi Ji; Yi-Ju Li; Joseph P Mathew; James P Daubert; Mihai V Podgoreanu Journal: Can J Anaesth Date: 2016-02-08 Impact factor: 5.063
Authors: Miklos D Kertai; Yi-Ju Li; Yunqi Ji; Wenjing Qi; Frederick W Lombard; Svati H Shah; William E Kraus; Mark Stafford-Smith; Mark F Newman; Carmelo A Milano; Nathan Waldron; Mihai V Podgoreanu; Joseph P Mathew Journal: Am Heart J Date: 2015-06-17 Impact factor: 4.749
Authors: Miklos D Kertai; Jonathan D Mosley; Jing He; Abinaya Ramakrishnan; Mark J Abdelmalak; Yurim Hong; M Benjamin Shoemaker; Dan M Roden; Lisa Bastarache Journal: Circ Genom Precis Med Date: 2021-03-01
Authors: Davor Lessel; Tariq Muhammad; Teresa Casar Tena; Barbara Moepps; Martin D Burkhalter; Marc-Phillip Hitz; Okan Toka; Axel Rentzsch; Stephan Schubert; Adelheid Schalinski; Ulrike M M Bauer; Christian Kubisch; Stephanie M Ware; Melanie Philipp Journal: Sci Rep Date: 2016-09-13 Impact factor: 4.379