Gain-of-function mutations in potassium channel subunit KCNE2 associated with early-onset lone atrial fibrillation

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Gain-of-function mutations in potassium channel subunit KCNE2 associated with early-onset lone atrial fibrillation. / Nielsen, Jonas Bille; Bentzen, Bo Hjorth; Olesen, Morten Salling; David, Jens-Peter; Olesen, Søren-Peter; Haunsø, Stig; Svendsen, Jesper Hastrup; Schmitt, Nicole.

In: Biomarkers in Medicine, Vol. 8, No. 4, 04.2014, p. 557-570.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Nielsen, JB, Bentzen, BH, Olesen, MS, David, J-P, Olesen, S-P, Haunsø, S, Svendsen, JH & Schmitt, N 2014, 'Gain-of-function mutations in potassium channel subunit KCNE2 associated with early-onset lone atrial fibrillation', Biomarkers in Medicine, vol. 8, no. 4, pp. 557-570. https://doi.org/10.2217/bmm.13.137

APA

Nielsen, J. B., Bentzen, B. H., Olesen, M. S., David, J-P., Olesen, S-P., Haunsø, S., ... Schmitt, N. (2014). Gain-of-function mutations in potassium channel subunit KCNE2 associated with early-onset lone atrial fibrillation. Biomarkers in Medicine, 8(4), 557-570. https://doi.org/10.2217/bmm.13.137

Vancouver

Nielsen JB, Bentzen BH, Olesen MS, David J-P, Olesen S-P, Haunsø S et al. Gain-of-function mutations in potassium channel subunit KCNE2 associated with early-onset lone atrial fibrillation. Biomarkers in Medicine. 2014 Apr;8(4):557-570. https://doi.org/10.2217/bmm.13.137

Author

Nielsen, Jonas Bille ; Bentzen, Bo Hjorth ; Olesen, Morten Salling ; David, Jens-Peter ; Olesen, Søren-Peter ; Haunsø, Stig ; Svendsen, Jesper Hastrup ; Schmitt, Nicole. / Gain-of-function mutations in potassium channel subunit KCNE2 associated with early-onset lone atrial fibrillation. In: Biomarkers in Medicine. 2014 ; Vol. 8, No. 4. pp. 557-570.

Bibtex

@article{a766dc7c43384cf5b70f41794ed995fc,
title = "Gain-of-function mutations in potassium channel subunit KCNE2 associated with early-onset lone atrial fibrillation",
abstract = "Aims: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Disturbances in cardiac potassium conductance are considered as one of the disease mechanisms in AF. We aimed to investigate if mutations in potassium-channel β-subunits KCNE2 and KCNE3 are associated with early-onset lone AF. Methods & results: The coding regions of KCNE2 and KCNE3 were bidirectionally sequenced in 192 unrelated patients diagnosed with early-onset lone AF (<40 years). Two nonsynonymous missense mutations were identified in KCNE2 (M23L and I57T). Both mutations were absent in a healthy control group (n = 1500 alleles). Electrophysiological investigations were performed for both mutations in combination with candidate pore-forming α-subunits KV7.1, KV11.1, KV4.3 and KV1.5. A significant gain-of-function effect was observed upon coexpression with KV7.1 and KV7.1 + KCNE1. Confocal imaging found no differences in subcellular localization. No disease-suspected mutations were identified in KCNE3. Conclusion: We identified two KCNE2 gain-of-function missense mutations that seem to increase the susceptibility of early-onset lone AF. These results confirm previous findings indicating that gain-of-function in the slow delayed rectifier potassium current might be involved in the pathogenesis of AF.",
author = "Nielsen, {Jonas Bille} and Bentzen, {Bo Hjorth} and Olesen, {Morten Salling} and Jens-Peter David and S{\o}ren-Peter Olesen and Stig Hauns{\o} and Svendsen, {Jesper Hastrup} and Nicole Schmitt",
year = "2014",
month = "4",
doi = "10.2217/bmm.13.137",
language = "English",
volume = "8",
pages = "557--570",
journal = "Biomarkers in Medicine",
issn = "1752-0363",
publisher = "Future Medicine Ltd.",
number = "4",

}

RIS

TY - JOUR

T1 - Gain-of-function mutations in potassium channel subunit KCNE2 associated with early-onset lone atrial fibrillation

AU - Nielsen, Jonas Bille

AU - Bentzen, Bo Hjorth

AU - Olesen, Morten Salling

AU - David, Jens-Peter

AU - Olesen, Søren-Peter

AU - Haunsø, Stig

AU - Svendsen, Jesper Hastrup

AU - Schmitt, Nicole

PY - 2014/4

Y1 - 2014/4

N2 - Aims: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Disturbances in cardiac potassium conductance are considered as one of the disease mechanisms in AF. We aimed to investigate if mutations in potassium-channel β-subunits KCNE2 and KCNE3 are associated with early-onset lone AF. Methods & results: The coding regions of KCNE2 and KCNE3 were bidirectionally sequenced in 192 unrelated patients diagnosed with early-onset lone AF (<40 years). Two nonsynonymous missense mutations were identified in KCNE2 (M23L and I57T). Both mutations were absent in a healthy control group (n = 1500 alleles). Electrophysiological investigations were performed for both mutations in combination with candidate pore-forming α-subunits KV7.1, KV11.1, KV4.3 and KV1.5. A significant gain-of-function effect was observed upon coexpression with KV7.1 and KV7.1 + KCNE1. Confocal imaging found no differences in subcellular localization. No disease-suspected mutations were identified in KCNE3. Conclusion: We identified two KCNE2 gain-of-function missense mutations that seem to increase the susceptibility of early-onset lone AF. These results confirm previous findings indicating that gain-of-function in the slow delayed rectifier potassium current might be involved in the pathogenesis of AF.

AB - Aims: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Disturbances in cardiac potassium conductance are considered as one of the disease mechanisms in AF. We aimed to investigate if mutations in potassium-channel β-subunits KCNE2 and KCNE3 are associated with early-onset lone AF. Methods & results: The coding regions of KCNE2 and KCNE3 were bidirectionally sequenced in 192 unrelated patients diagnosed with early-onset lone AF (<40 years). Two nonsynonymous missense mutations were identified in KCNE2 (M23L and I57T). Both mutations were absent in a healthy control group (n = 1500 alleles). Electrophysiological investigations were performed for both mutations in combination with candidate pore-forming α-subunits KV7.1, KV11.1, KV4.3 and KV1.5. A significant gain-of-function effect was observed upon coexpression with KV7.1 and KV7.1 + KCNE1. Confocal imaging found no differences in subcellular localization. No disease-suspected mutations were identified in KCNE3. Conclusion: We identified two KCNE2 gain-of-function missense mutations that seem to increase the susceptibility of early-onset lone AF. These results confirm previous findings indicating that gain-of-function in the slow delayed rectifier potassium current might be involved in the pathogenesis of AF.

U2 - 10.2217/bmm.13.137

DO - 10.2217/bmm.13.137

M3 - Journal article

C2 - 24796621

VL - 8

SP - 557

EP - 570

JO - Biomarkers in Medicine

JF - Biomarkers in Medicine

SN - 1752-0363

IS - 4

ER -

ID: 113183476