Referenced in: none

Automatically associated channels: Kir2.3 , Nav1.5

Title: A common polymorphism in SCN5A is associated with lone atrial fibrillation.

Authors: L Y Chen, J D Ballew, K J Herron, R J Rodeheffer, T M Olson

Journal, date & volume: Clin. Pharmacol. Ther., 2007 Jan , 81, 35-41

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/17185997

Abstract
The cardiac sodium channel (SCN5A) is a target for the treatment of arrhythmias. We hypothesized that vulnerability to atrial fibrillation (AF) could be caused by genetic variation in SCN5A. We recruited 157 patients with early-onset AF who lacked traditional risk factors, and 314 matched controls. SCN5A was subject to targeted genotyping of a common loss-of-function H558R polymorphism and comprehensive mutation scanning. Genotype frequencies in the AF cohort vs controls were as follows: HH, 50 vs 63%; HR, 40 vs 33%; and RR, 10 vs 4% (P=0.008). Additional coding sequence mutations were ruled out. The R558 allele was more common in patients than in controls (30 vs 21%, P=0.002), conferring an odds ratios for AF of 1.6 (95% confidence interval 1.2-2.2). The SCN5A R558 allele, present in one-third of the population, thus constitutes a risk factor for lone AF and may increase susceptibility to sodium channel blocker-induced proarrhythmia.