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

Federico Denti; Christian Paludan-Müller; Søren-Peter Olesen; Stig Haunsø; Jesper Hastrup Svendsen; Morten Salling Olesen; Bo Hjorth Bentzen; Nicole Schmitt

doi:10.2217/pme-2017-0076

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

Federico Denti, Christian Paludan-Müller, Søren-Peter Olesen, Stig Haunsø, Jesper Hastrup Svendsen, Morten Salling Olesen, Bo Hjorth Bentzen, Nicole Schmitt

Research output: Contribution to journal › Journal article › Research › peer-review

4 Citations (Scopus)

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.

Original language	English
Journal	Personalized Medicine
Volume	15
Issue number	2
Pages (from-to)	93-102
Number of pages	10
ISSN	1741-0541
DOIs	https://doi.org/10.2217/pme-2017-0076
Publication status	Published - Mar 2018

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10.2217/pme-2017-0076

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Functional consequences of genetic variation in sodium channel modifiers in early onset lone atrial fibrillation. / Denti, Federico; Paludan-Müller, Christian; Olesen, Søren-Peter; Haunsø, Stig ; Svendsen, Jesper Hastrup ; Olesen, Morten Salling ; Bentzen, Bo Hjorth ; Schmitt, Nicole.

In: Personalized Medicine, Vol. 15, No. 2, 03.2018, p. 93-102.

Research output: Contribution to journal › Journal article › Research › peer-review

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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.",

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AU - Denti, Federico

AU - Paludan-Müller, Christian

AU - Olesen, Søren-Peter

AU - Haunsø, Stig

AU - Svendsen, Jesper Hastrup

AU - Olesen, Morten Salling

AU - Bentzen, Bo Hjorth

AU - Schmitt, Nicole

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N2 - 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.

AB - 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.

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DO - 10.2217/pme-2017-0076

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