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

Per Med. 2018 Mar;15(2):93-102. doi: 10.2217/pme-2017-0076. Epub 2018 Jan 31.

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.

Keywords: atrial fibrillation; cardiac sodium current; sodium channel ancillary subunit.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / genetics*
  • Atrial Fibrillation / metabolism
  • Calcium-Binding Proteins / genetics*
  • Calcium-Binding Proteins / metabolism
  • DNA Mutational Analysis / methods
  • Denmark
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genetic Testing / methods
  • Genetic Variation / genetics
  • Glycerolphosphate Dehydrogenase / genetics*
  • Glycerolphosphate Dehydrogenase / metabolism
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Middle Aged
  • Muscle Proteins / genetics*
  • Muscle Proteins / metabolism
  • Mutation
  • Sodium Channels / genetics

Substances

  • Calcium-Binding Proteins
  • Membrane Proteins
  • Muscle Proteins
  • Sodium Channels
  • syntrophin alpha1
  • GPD1L protein, human
  • Glycerolphosphate Dehydrogenase