Common and Rare Variants in SCN10A Modulate the Risk of Atrial Fibrillation

Abstract

Background-Genome-wide association studies (GWAS) have shown that the common single nucleotide polymorphism (SNP) rs6800541 located in SCN10A, encoding the voltage-gated Na v 1.8 sodium channel, is associated with PR-interval prolongation and atrial fibrillation (AF).SNP rs6800541 is in high linkage disequilibrium with the non-synonymous variant in SCN10A, rs6795970 (V1073A, r 2 =0.933).We therefore sought to determine whether common and rare SCN10A variants are associated with early onset AF.Methods and Results-SCN10A was sequenced in 225 AF patients in whom there was no evidence of other cardiovascular disease or dysfunction (lone AF).In an association study of the rs6795970 SNP variant, we included 515 AF patients, and two control cohorts of 730 individuals free of AF and 6,161 randomly sampled individuals.Functional characterization of SCN10A variants was performed by whole-cell patch-clamping.In the lone AF cohort, nine rare missense