Both Common and Rare SCN10A Variants Associated with Brugada Syndrome Displayed an Increase in Late Nav1.8 Sodium Currents in ND 7/23 cells

Introduction: Brugada syndrome (BrS) is an oligogenic disease, often linked to mutations in SCN5A encoding the canonical cardiac sodium channel. Prolongation of QRS interval implicates slowed cardiac conduction as an important element of the BrS arrhythmia phenotype. Recent genome-wide association studies have implicated common variation in SCN10A as a potential modulator of cardiac conduction. SCN10A encodes the tetrodotoxin-resistant voltage-gated sodium channel isoform Nav1.8 primarily found in dorsal root ganglia and at lower levels in the heart. A recent candidate gene sequencing study identified 5 non-synonymous SCN10A rare variants in 4/156 white SCN5A mutation-negative patients with BrS and one protective non-synonymous common variant V1073A [(T>C): T allele BrS vs. control: 65.1% vs. 40.1%, P = 3.54x10-19]. Hypothesis: Here we tested the hypothesis that the common variant (V1073A) and 2 of the rare variants identified (A200V, I671V) generate aberrant Nav1.8 function and this may contribute to BrS...