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Am Heart J. 2014 Jan;167(1):101-108.e1. doi: 10.1016/j.ahj.2013.09.016. Epub 2013 Oct 17.

Genetic variation in the β1-adrenergic receptor is associated with the risk of atrial fibrillation after cardiac surgery.

Author information

  • 1Center for Human Genetics Research, Vanderbilt University, Nashville, TN.
  • 2Department of Anesthesiology, Vanderbilt University, Nashville, TN.
  • 3Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University, Nashville, TN.
  • 4Center for Human Genetics Research, Vanderbilt University, Nashville, TN; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN.
  • 5Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University, Nashville, TN; Institute of Clinical Pharmacology and Toxicology, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: daniel.kurnik@vanderbilt.edu.

Abstract

BACKGROUND:

Postoperative atrial fibrillation (PoAF) after cardiac surgery is common and associated with increased morbidity and mortality. Increased sympathetic activation after surgery contributes to PoAF, and β-blockers are the first-line recommendation for its prevention. We examined the hypothesis that common functional genetic variants in the β1-adrenoreceptor, the mediator of cardiac sympathetic activation and drug target of β-blockers, are associated with the risk for PoAF and with the protective effect of β-blockers.

METHODS:

In a prospective cohort study, we studied 947 adult European Americans who underwent cardiac surgery at Vanderbilt University between 1999 and 2005. We genotyped 2 variants in the β1-adrenoreceptor, rs1801253 (Arg389Gly) and rs1801252 (Ser49Gly), and used logistic regression to examine the association between genotypes and PoAF occurring within 14 days after surgery, before and after adjustment for demographic and clinical covariates.

RESULTS:

Postoperative atrial fibrillation occurred in 239 patients (25.2%) and was associated with rs1801253 genotype (adjusted P = .008), with Gly389Gly having an odds ratio of 2.63 (95% CI 1.42-4.89) for PoAF compared to the common Arg389Arg (P = .002). In a predefined subgroup analysis, this association appeared to be stronger among patients without β-blocker prophylaxis (adjusted odds ratio 7.00, 95% CI 1.82-26.96, P = .005) compared to patients with β-blocker prophylaxis, among whom the association between rs1801253 genotype and PoAF was not statistically significant (adjusted P = .11).

CONCLUSION:

The Gly389 variant in the β1-adrenoreceptor is associated with PoAF, and this association appears to be modulated by β-blocker therapy. Future studies of the association of other adrenergic pathway genes with PoAF will be of interest.

© 2014.

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