title: Beta1-adrenoceptor polymorphism predicts flecainide action in patients with atrial fibrillation.
abstract: BACKGROUND
  Antiarrhythmic action of flecainide is based on sodium channel blockade. Beta(1)-adrenoceptor (beta(1)AR) activation induces sodium channel inhibition, too. The aim of the present study was to evaluate the impact of different beta(1)AR genotypes on antiarrhythmic action of flecainide in patients with structural heart disease and atrial fibrillation.
  
  
  RESULTS
  In 145 subjects, 87 with atrial fibrillation, genotyping was performed to identify the individual beta(1)AR Arg389Gly and Ser49Gly polymorphism. Resting heart rate during atrial fibrillation and success of flecainide-induced cardioversion were correlated with beta(1)AR genotype. The overall cardioversion rate with flecainide was 39%. The Arg389Arg genotype was associated with the highest cardioversion rate (55.5%; OR 3.30; 95% CI; 1.34-8.13; p = 0.003) compared to patients with Arg389Gly (29.5%; OR 0.44; 95% CI; 0.18-1.06; p = 0.066) and Gly389Gly (14%; OR 0.24; 95% CI 0.03-2.07; p = 0.17) variants. The single Ser49Gly polymorphism did not influence the conversion rate. In combination, patients with Arg389Gly-Ser49Gly genotype displayed the lowest conversion rate with 20.8% (OR 0.31; 95% CI; 0.10-0.93; p = 0.03). In patients with Arg389Arg variants the heart rate during atrial fibrillation was significantly higher (110+/-2.7 bpm; p = 0.03 vs. other variants) compared to Arg389Gly (104.8+/-2.4 bpm) and Gly389Gly (96.9+/-5.8 bpm) carriers. The Arg389Gly-Ser49Gly genotype was more common in patients with atrial fibrillation compared to patients without atrial fibrillation (27.6% vs. 5.2%; HR 6.98; 95% CI; 1.99-24.46; p<0.001).
  
  
  CONCLUSIONS
  The beta(1)AR Arg389Arg genotype is associated with increased flecainide potency and higher heart rate during atrial fibrillation. The Arg389Gly-Ser49Gly genotype might be of predictive value for atrial fibrillation.
authors.affiliation: Department of Internal Medicine III, University of Cologne, Cologne, Germany.
authors.forename: Amir M
authors.initials: AM
authors.lastname: Nia
authors.forename: Evren
authors.initials: E
authors.lastname: Caglayan
authors.forename: Natig
authors.initials: N
authors.lastname: Gassanov
authors.forename: Tom
authors.initials: T
authors.lastname: Zimmermann
authors.forename: Orhan
authors.initials: O
authors.lastname: Aslan
authors.forename: Martin
authors.initials: M
authors.lastname: Hellmich
authors.forename: Firat
authors.initials: F
authors.lastname: Duru
authors.forename: Erland
authors.initials: E
authors.lastname: Erdmann
authors.forename: Stephan
authors.initials: S
authors.lastname: Rosenkranz
authors.forename: Fikret
authors.initials: F
authors.lastname: Er
mesh_terms: D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000235:genetics*; D004452:Echocardiography; D005260:Female; D005424:Flecainide / Q000627:therapeutic use*; D005838:Genotype; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*
chemical_list: D000889:Anti-Arrhythmia Agents; D018342:Receptors, Adrenergic, beta-1; D005424:Flecainide