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

Abstract

Aim: We investigated the effect of variants in genes encoding sodium channel modifiers SNTA1 and GPD1L found in early onset atrial fibrillation (AF) patients. Patients & methods: 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. Results: 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 -5 mV. The SNTA1-p.A257G variant significantly increased INa. SNTA1-p.P74L did not produce functional changes. Conclusion: 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.