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

2 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Personalized Medicine
Vol/bind	15
Udgave nummer	2
Sider (fra-til)	93-102
Antal sider	10
ISSN	1741-0541
DOI	https://doi.org/10.2217/pme-2017-0076
Status	Udgivet - mar. 2018

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10.2217/pme-2017-0076

Citationsformater

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title = "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.",

author = "Federico Denti and Christian Paludan-M{\"u}ller and S{\o}ren-Peter Olesen and Stig Hauns{\o} and Svendsen, {Jesper Hastrup} and Olesen, {Morten Salling} and Bentzen, {Bo Hjorth} and Nicole Schmitt",

year = "2018",

month = mar,

doi = "10.2217/pme-2017-0076",

language = "English",

volume = "15",

pages = "93--102",

journal = "Personalized Medicine",

issn = "1741-0541",

publisher = "Future Medicine Ltd.",

number = "2",

}

TY - JOUR

T1 - Functional consequences of genetic variation in sodium channel modifiers in early onset lone atrial fibrillation

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

PY - 2018/3

Y1 - 2018/3

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.

U2 - 10.2217/pme-2017-0076

DO - 10.2217/pme-2017-0076

M3 - Journal article

C2 - 29714131

SN - 1741-0541

VL - 15

SP - 93

EP - 102

JO - Personalized Medicine

JF - Personalized Medicine

IS - 2

ER -

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

Abstract

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