G protein-coupled receptor kinase 5 gene polymorphisms are associated with postoperative atrial fibrillation after coronary artery bypass grafting in patients receiving β-blockers.
G protein-coupled receptor kinase 5 gene polymorphisms are associated with postoperative atrial fibrillation after coronary artery bypass grafting in patients receiving β-blockers.
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DOI：
10.1161/circgenetics.113.000451
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发表时间：
2014-10
期刊：
影响因子：
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通讯作者：
Duke Perioperative Genetics and Safety Outcomes (PEGASUS) Investigative Team
中科院分区：
文献类型：
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作者：
Kertai MD;Li YW;Li YJ;Shah SH;Kraus WE;Fontes ML;Stafford-Smith M;Newman MF;Podgoreanu MV;Mathew JP;Duke Perioperative Genetics and Safety Outcomes (PEGASUS) Investigative Team
We hypothesized that genetic variations in the adrenergic signaling pathway and cytochrome P450 (CYP) 2D6 enzyme are associated with new-onset atrial fibrillation (AF) in patients who underwent coronary artery bypass graft (CABG) surgery and were treated with perioperative beta-blocker (BB). Two cohorts of patients who underwent CABG surgery 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 CYP2D6 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 (CATHGEN) 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=0.007-0.016). However, meta-analysis of the two datasets 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). In patients undergoing CABG surgery, genetic variation in GRK5 is associated with postoperative AF despite perioperative BB therapy.
