A common polymorphism in SCN5A is associated with lone atrial fibrillation

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

Research output: Contribution to journalArticlepeer-review

144 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)35-41
Number of pages7
JournalClinical pharmacology and therapeutics
Issue number1
StatePublished - Jan 2007


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