title: A common polymorphism in SCN5A is associated with lone atrial fibrillation.
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.
authors.affiliation: Department of Medicine, Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors.forename: L Y
authors.initials: LY
authors.lastname: Chen
authors.forename: J D
authors.initials: JD
authors.lastname: Ballew
authors.forename: K J
authors.initials: KJ
authors.lastname: Herron
authors.forename: R J
authors.initials: RJ
authors.lastname: Rodeheffer
authors.forename: T M
authors.initials: TM
authors.lastname: Olson
mesh_terms: D001281:Atrial Fibrillation / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D062554:NAV1.5 Voltage-Gated Sodium Channel; D011110:Polymorphism, Genetic; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels