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

Publication ,  Other
Kertai, MD; Li, Y-W; Li, Y-J; Shah, SH; Kraus, WE; Fontes, ML; Stafford-Smith, M; Newman, MF; Podgoreanu, MV; Mathew, JP ...
Published in: Circ Cardiovasc Genet
October 2014

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.

Duke Scholars

Published In

Circ Cardiovasc Genet

DOI

EISSN

1942-3268

Publication Date

October 2014

Volume

7

Issue

5

Start / End Page

625 / 633

Location

United States

Related Subject Headings

  • Signal Transduction
  • Postoperative Complications
  • Polymorphism, Single Nucleotide
  • Odds Ratio
  • Middle Aged
  • Male
  • Linkage Disequilibrium
  • Humans
  • Haplotypes
  • Genetic Variation
 

Citation

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Kertai, M. D., Li, Y.-W., Li, Y.-J., Shah, S. H., Kraus, W. E., Fontes, M. L., … Duke Perioperative Genetics and Safety Outcomes (PEGASUS) Investigative Team. (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. Circ Cardiovasc Genet. United States. https://doi.org/10.1161/CIRCGENETICS.113.000451

Published In

Circ Cardiovasc Genet

DOI

EISSN

1942-3268

Publication Date

October 2014

Volume

7

Issue

5

Start / End Page

625 / 633

Location

United States

Related Subject Headings

  • Signal Transduction
  • Postoperative Complications
  • Polymorphism, Single Nucleotide
  • Odds Ratio
  • Middle Aged
  • Male
  • Linkage Disequilibrium
  • Humans
  • Haplotypes
  • Genetic Variation