SCN5A promoter haplotype affects the therapeutic range for serum flecainide concentration in Asian patients
Open Access
- 1 July 2013
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Pharmacogenetics and Genomics
- Vol. 23 (7), 349-354
- https://doi.org/10.1097/fpc.0b013e328361fb8d
Abstract
Objective An increased slowing of cardiac conduction induced by sodium channel blockers is remarkably observed in carriers of an Asian-specific promoter haplotype [haplotype B (HapB)] of the cardiac sodium channel gene (SCN5A). We investigated the effect of HapB on the therapeutic range for serum flecainide concentration in Asian patients. Patients and methods We examined the serum concentration and antiarrhythmic efficacy of flecainide, together with the SCN5A promoter haplotype, in 146 patients with supraventricular tachyarrhythmias. Trough serum flecainide concentrations were determined by HPLC. The antiarrhythmic efficacy of flecainide was assessed for at least 2 months through examination of symptomatology, ECG, and Holter monitoring. Results The serum flecainide concentration did not differ between the wild-type HapA homozygotes and HapB carriers under treatment with the usual dose. A genetic difference in the antiarrhythmic efficacy of flecainide was observed between the HapA homozygotes and HapB carriers at serum flecainide concentrations less than 300 ng/ml (42.9 vs. 68.8%; P=0.022). PR prolongation and QRS widening were observed more commonly among the HapB carriers with serum flecainide concentrations of at least 300 ng/ml than in the HapA homozygotes (PR, 210±25 vs. 195±25 ms; P=0.036; and QRS, 112±10 vs. 105±9 ms; P=0.030). Conclusion These findings suggest that the therapeutic range for serum flecainide concentration is lower in HapB carriers than in HapA homozygotes.Keywords
This publication has 29 references indexed in Scilit:
- High Prevalence of Long QT Syndrome–Associated SCN5A Variants in Patients With Early-Onset Lone Atrial FibrillationCirculation: Cardiovascular Genetics, 2012
- Polymorphism H558R in the Human Cardiac Sodium Channel SCN5A Gene is Associated with Atrial FibrillationJournal of International Medical Research, 2011
- REVIEW: Sodium Channel (Dys)Function and Cardiac ArrhythmiasCardiovascular Therapeutics, 2010
- Inherited Cardiac Diseases Caused by Mutations in the Nav1.5 Sodium ChannelJournal of Cardiovascular Electrophysiology, 2009
- A Common Polymorphism in SCN5A is Associated with Lone Atrial FibrillationClinical Pharmacology & Therapeutics, 2007
- Sodium Channel Mutations and Susceptibility to Heart Failure and Atrial FibrillationJAMA, 2005
- SCN5A Mutation Associated With Dilated Cardiomyopathy, Conduction Disorder, and ArrhythmiaCirculation, 2004
- Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A)JCI Insight, 2003
- Altered atrial, atrioventricular, and ventricular conduction in patients with the long QT syndrome caused by the ΔKPQ SCN5A sodium channel gene mutationThe American Journal of Cardiology, 2001
- Antiarrhythmic drugs and cardiac ion channels: mechanisms of actionProgress in Biophysics and Molecular Biology, 1998