Functional consequences of genetic variation in sodium channel modifiers in early onset lone atrial fibrillation.

Abstract

We investigated the effect of variants in genes encoding sodium channel modifiers SNTA1 and GPD1L found in early onset atrial fibrillation (AF) patients. Genetic screening in patients with early onset lone AF revealed three variants in GPD1L and SNTA1 in three AF patients. Functional analysis was performed by patch-clamp electrophysiology. Co-expression of GPD1L or its p.A326E variant with NaV1.5 did not alter INa density or current kinetics. SNTA1 shifted the peak-current by -5mV. The SNTA1-p.A257G variant significantly increased INa. SNTA1-p.P74L did not produce functional changes. Although genetic variation of sodium channel modifiers may contribute to development of AF at a molecular level, it is unlikely a monogenic cause of the disease.