title: Genetic variation in the β1-adrenergic receptor is associated with the risk of atrial fibrillation after cardiac surgery.
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).
  
  
  CONCLUSIONS
  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.
authors: Center for Human Genetics Research, Vanderbilt University, Nashville, TN.
authors: Janina M
authors: JM
authors: Jeff
authors: Department of Anesthesiology, Vanderbilt University, Nashville, TN.
authors: Brian S
authors: BS
authors: Donahue
authors: Center for Human Genetics Research, Vanderbilt University, Nashville, TN.
authors: Kristin
authors: K
authors: Brown-Gentry
authors: Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University, Nashville, TN.
authors: Dan M
authors: DM
authors: Roden
authors: Center for Human Genetics Research, Vanderbilt University, Nashville, TN; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN.
authors: Dana C
authors: DC
authors: Crawford
authors: Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University, Nashville, TN.
authors: C Michael
authors: CM
authors: Stein
authors: Division 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.
authors: Daniel
authors: D
authors: Kurnik
mesh_terms: D000328:Adult; D000368:Aged; D001281:Atrial Fibrillation / Q000453:epidemiology / Q000235:genetics* / Q000601:surgery; D006348:Cardiac Surgical Procedures; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications / Q000235:genetics* / Q000517:prevention & control; D011446:Prospective Studies; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: C547787:ADRB1 protein, human; D018342:Receptors, Adrenergic, beta-1