title: β1-Adrenergic receptor Arg389Gly polymorphism affects the antiarrhythmic efficacy of flecainide in patients with coadministration of β-blockers.
abstract: OBJECTIVE
  β1-Adrenergic receptor (β1-AR) stimulation modulates the antiarrhythmic activities of sodium channel blockers. The β1-AR Gly389 variant shows a marked decrease in agonist-stimulated cyclic AMP production compared with that of the wild-type Arg389 in vitro. We investigated whether the Arg389Gly polymorphism affects the efficacy of flecainide, a typical sodium channel blocker, in patients with or without coadministration of β-blockers.
  
  
  METHODS
  The effects of the β1-AR Arg389Gly polymorphism on the antiarrhythmic efficacy of flecainide were compared between with and without coadministered β-blockers in 159 patients with supraventricular tachyarrhythmia. The antiarrhythmic efficacy of flecainide was assessed for at least 2 months by evaluating symptomatology, 12-lead ECGs, and Holter monitoring results.
  
  
  RESULTS
  Genetic differences in the antiarrhythmic efficacy of flecainide were observed in patients with coadministration of β-blockers. Tachyarrhythmia was well controlled in 60% of Arg389-homozygotes, 30% of Gly389-heterozygotes, and 0% of Gly389-homozygotes (P=0.001). In contrast, no difference in the antiarrhythmic efficacy was observed among the three genotypes in the patients without coadministration of β-blockers (64, 70, and 60%, respectively). Heart rate in tachyarrhythmia in patients treated with flecainide was significantly higher in Gly389 carriers than in Arg389-homozygotes (P=0.013).
  
  
  CONCLUSIONS
  The Gly389 polymorphism decreased the antiarrhythmic efficacy of flecainide when coadministered with β-blockers. The results indicate that the Arg389Gly polymorphism may play an important role in predicting the efficacy of flecainide in patients with coadministration of β-blockers.
authors: Departments of aPharmaceutical Sciences bInternal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors: Kosuke
authors: K
authors: Doki
authors: Yukio
authors: Y
authors: Sekiguchi
authors: Keisuke
authors: K
authors: Kuga
authors: Kazutaka
authors: K
authors: Aonuma
authors: Masato
authors: M
authors: Homma
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000627:therapeutic use; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005424:Flecainide / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071184:Pharmacogenomic Variants; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D013617:Tachycardia, Supraventricular / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D018342:Receptors, Adrenergic, beta-1; D005424:Flecainide