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).

CONCLUSION:

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: Kosuke Doki, Yukio Sekiguchi, Keisuke Kuga, Kazutaka Aonuma, Masato Homma
• Journal: Pharmacogenetics and genomics (Pharmacogenet Genomics) Vol. 26 Issue 10 Pg. 481-5 (Oct 2016) ISSN: 1744-6880 [Electronic] United States
• PMID: 27500822 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Adrenergic beta-Antagonists
• Anti-Arrhythmia Agents
• Receptors, Adrenergic, beta-1
• Flecainide

Topics

• Adrenergic beta-Antagonists (administration & dosage, therapeutic use)
• Aged
• Anti-Arrhythmia Agents (administration & dosage, therapeutic use)
• Drug Therapy, Combination
• Female
• Flecainide (administration & dosage, therapeutic use)
• Humans
• Male
• Middle Aged
• Pharmacogenomic Variants
• Receptors, Adrenergic, beta-1 (genetics)
• Tachycardia, Supraventricular (drug therapy)
• Treatment Outcome