1. Functional consequences of genetic variation in sodium channel modifiers in early onset lone atrial fibrillation.
- Author
-
Denti F, Paludan-Müller C, Olesen SP, Haunsø S, Svendsen JH, Olesen MS, Bentzen BH, and Schmitt N
- Subjects
- Adult, Aged, Aged, 80 and over, Atrial Fibrillation diagnosis, Atrial Fibrillation metabolism, Calcium-Binding Proteins metabolism, DNA Mutational Analysis methods, Denmark, Female, Genetic Predisposition to Disease genetics, Genetic Testing methods, Genetic Variation genetics, Glycerolphosphate Dehydrogenase metabolism, Humans, Male, Membrane Proteins metabolism, Middle Aged, Muscle Proteins metabolism, Mutation, Sodium Channels genetics, Atrial Fibrillation genetics, Calcium-Binding Proteins genetics, Glycerolphosphate Dehydrogenase genetics, Membrane Proteins genetics, Muscle Proteins genetics
- 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 Na
V 1.5 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.- Published
- 2018
- Full Text
- View/download PDF