G protein-coupled receptor kinase 5 gene polymorphisms are associated with postoperative atrial fibrillation after coronary artery bypass grafting in patients receiving β-blockers.
Other Article (Journal Article)
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.
Full Text
Duke Authors
- Gaca, Jeffrey Giles
- Ginsburg, Geoffrey Steven
- Glower Jr., Donald D.
- Hauser, Elizabeth Rebecca
- Kraus, William Erle
- Laskowitz, Daniel Todd
- Li, Yi-Ju
- Mathew, Joseph P.
- Milano, Carmelo Alessio
- Newman, Mark Franklin
- Podgoreanu, Mihai V.
- Shah, Svati Hasmukh
- Smith, Peter Kent
- Stafford-Smith, Mark
- Swaminathan, Madhav
- Welsby, Ian James
Cited Authors
- Kertai, MD; Li, Y-W; Li, Y-J; Shah, SH; Kraus, WE; Fontes, ML; Stafford-Smith, M; Newman, MF; Podgoreanu, MV; Mathew, JP; Duke Perioperative Genetics and Safety Outcomes (PEGASUS) Investigative Team,
Published Date
- October 2014
Published In
Volume / Issue
- 7 / 5
Start / End Page
- 625 - 633
PubMed ID
- 25049040
Electronic International Standard Serial Number (EISSN)
- 1942-3268
Digital Object Identifier (DOI)
- 10.1161/CIRCGENETICS.113.000451
Language
- eng
Conference Location
- United States