KCNN2 polymorphisms and cardiac tachyarrhythmias

Chih Chieh Yu, Tsai Chia-Ti, Pei Lung Chen, Cho Kai Wu, Fu Chun Chiu, Fu Tien Chiang, Peng Sheng Chen, Chi Ling Chen, Lian Yu Lin, Jyh Ming Juang, Li Ting Ho, Ling Ping La, Wei Shiung Yang, Jiunn Lee Lin

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Potassium calcium-activated channel subfamily N member 2 (KCNN2) encodes an integral membrane protein that forms smallconductance calcium-activated potassium (SK) channels. Recent studies in animal models show that SK channels are important in atrial and ventricular repolarization and arrhythmogenesis. However, the importance of SK channels in human arrhythmia remains unclear. The purpose of the present study was to test the association between genetic polymorphism of the SK2 channel and the occurrence of cardiac tachyarrhythmias in humans. We enrolled 327 Han Chinese, including 72 with clinically significant ventricular tachyarrhythmias (VTa) who had a history of aborted sudden cardiac death (SCD) or unexplained syncope, 98 with a history of atrial fibrillation (AF), and 144 normal controls. We genotyped 12 representative tag single nucleotide polymorphisms (SNPs) across a 141-kb genetic region containing the KCNN2 gene; these captured the full haplotype information. The rs13184658 and rs10076582 variants of KCNN2 were associated with VTa in both the additive and dominant models (odds ratio [OR] 2.89, 95% confidence interval [CI]=1.505-5.545, P=0.001; and OR 2.55, 95% CI=1.428-4.566, P=0.002, respectively). After adjustment for potential risk factors, the association remained significant. The population attributable risks of these 2 variants of VTa were 17.3% and 10.6%, respectively. One variant (rs13184658) showed weak but significant association with AF in a dominant model (OR 1.91, CI= 1.025-3.570], P=0.042). There was a significant association between the KCNN2 variants and clinically significant VTa. These findings suggest an association between KCNN2 and VTa; it also appears that KCNN2 variants may be adjunctive markers for risk stratification in patients susceptible to SCD.

Original languageEnglish
Article numbere4312
JournalMedicine (United States)
Volume95
Issue number29
DOIs
Publication statusPublished - Jul 26 2016
Externally publishedYes

Fingerprint

Tachycardia
Calcium-Activated Potassium Channels
Odds Ratio
Sudden Cardiac Death
Confidence Intervals
Atrial Fibrillation
Syncope
Genetic Polymorphisms
Haplotypes
Single Nucleotide Polymorphism
Cardiac Arrhythmias
Membrane Proteins
Animal Models
Population
Genes

Keywords

  • Association studies
  • Genetics
  • Heart arrest
  • Ion channel
  • Risk prediction
  • Ventricular arrhythmia

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Yu, C. C., Chia-Ti, T., Chen, P. L., Wu, C. K., Chiu, F. C., Chiang, F. T., ... Lin, J. L. (2016). KCNN2 polymorphisms and cardiac tachyarrhythmias. Medicine (United States), 95(29), [e4312]. https://doi.org/10.1097/MD.0000000000004312

KCNN2 polymorphisms and cardiac tachyarrhythmias. / Yu, Chih Chieh; Chia-Ti, Tsai; Chen, Pei Lung; Wu, Cho Kai; Chiu, Fu Chun; Chiang, Fu Tien; Chen, Peng Sheng; Chen, Chi Ling; Lin, Lian Yu; Juang, Jyh Ming; Ho, Li Ting; La, Ling Ping; Yang, Wei Shiung; Lin, Jiunn Lee.

In: Medicine (United States), Vol. 95, No. 29, e4312, 26.07.2016.

Research output: Contribution to journalArticle

Yu, CC, Chia-Ti, T, Chen, PL, Wu, CK, Chiu, FC, Chiang, FT, Chen, PS, Chen, CL, Lin, LY, Juang, JM, Ho, LT, La, LP, Yang, WS & Lin, JL 2016, 'KCNN2 polymorphisms and cardiac tachyarrhythmias', Medicine (United States), vol. 95, no. 29, e4312. https://doi.org/10.1097/MD.0000000000004312
Yu CC, Chia-Ti T, Chen PL, Wu CK, Chiu FC, Chiang FT et al. KCNN2 polymorphisms and cardiac tachyarrhythmias. Medicine (United States). 2016 Jul 26;95(29). e4312. https://doi.org/10.1097/MD.0000000000004312
Yu, Chih Chieh ; Chia-Ti, Tsai ; Chen, Pei Lung ; Wu, Cho Kai ; Chiu, Fu Chun ; Chiang, Fu Tien ; Chen, Peng Sheng ; Chen, Chi Ling ; Lin, Lian Yu ; Juang, Jyh Ming ; Ho, Li Ting ; La, Ling Ping ; Yang, Wei Shiung ; Lin, Jiunn Lee. / KCNN2 polymorphisms and cardiac tachyarrhythmias. In: Medicine (United States). 2016 ; Vol. 95, No. 29.
@article{25b06145a6094d6aa21cd136ec8758c8,
title = "KCNN2 polymorphisms and cardiac tachyarrhythmias",
abstract = "Potassium calcium-activated channel subfamily N member 2 (KCNN2) encodes an integral membrane protein that forms smallconductance calcium-activated potassium (SK) channels. Recent studies in animal models show that SK channels are important in atrial and ventricular repolarization and arrhythmogenesis. However, the importance of SK channels in human arrhythmia remains unclear. The purpose of the present study was to test the association between genetic polymorphism of the SK2 channel and the occurrence of cardiac tachyarrhythmias in humans. We enrolled 327 Han Chinese, including 72 with clinically significant ventricular tachyarrhythmias (VTa) who had a history of aborted sudden cardiac death (SCD) or unexplained syncope, 98 with a history of atrial fibrillation (AF), and 144 normal controls. We genotyped 12 representative tag single nucleotide polymorphisms (SNPs) across a 141-kb genetic region containing the KCNN2 gene; these captured the full haplotype information. The rs13184658 and rs10076582 variants of KCNN2 were associated with VTa in both the additive and dominant models (odds ratio [OR] 2.89, 95{\%} confidence interval [CI]=1.505-5.545, P=0.001; and OR 2.55, 95{\%} CI=1.428-4.566, P=0.002, respectively). After adjustment for potential risk factors, the association remained significant. The population attributable risks of these 2 variants of VTa were 17.3{\%} and 10.6{\%}, respectively. One variant (rs13184658) showed weak but significant association with AF in a dominant model (OR 1.91, CI= 1.025-3.570], P=0.042). There was a significant association between the KCNN2 variants and clinically significant VTa. These findings suggest an association between KCNN2 and VTa; it also appears that KCNN2 variants may be adjunctive markers for risk stratification in patients susceptible to SCD.",
keywords = "Association studies, Genetics, Heart arrest, Ion channel, Risk prediction, Ventricular arrhythmia",
author = "Yu, {Chih Chieh} and Tsai Chia-Ti and Chen, {Pei Lung} and Wu, {Cho Kai} and Chiu, {Fu Chun} and Chiang, {Fu Tien} and Chen, {Peng Sheng} and Chen, {Chi Ling} and Lin, {Lian Yu} and Juang, {Jyh Ming} and Ho, {Li Ting} and La, {Ling Ping} and Yang, {Wei Shiung} and Lin, {Jiunn Lee}",
year = "2016",
month = "7",
day = "26",
doi = "10.1097/MD.0000000000004312",
language = "English",
volume = "95",
journal = "Medicine; analytical reviews of general medicine, neurology, psychiatry, dermatology, and pediatries",
issn = "0025-7974",
publisher = "Lippincott Williams and Wilkins",
number = "29",

}

TY - JOUR

T1 - KCNN2 polymorphisms and cardiac tachyarrhythmias

AU - Yu, Chih Chieh

AU - Chia-Ti, Tsai

AU - Chen, Pei Lung

AU - Wu, Cho Kai

AU - Chiu, Fu Chun

AU - Chiang, Fu Tien

AU - Chen, Peng Sheng

AU - Chen, Chi Ling

AU - Lin, Lian Yu

AU - Juang, Jyh Ming

AU - Ho, Li Ting

AU - La, Ling Ping

AU - Yang, Wei Shiung

AU - Lin, Jiunn Lee

PY - 2016/7/26

Y1 - 2016/7/26

N2 - Potassium calcium-activated channel subfamily N member 2 (KCNN2) encodes an integral membrane protein that forms smallconductance calcium-activated potassium (SK) channels. Recent studies in animal models show that SK channels are important in atrial and ventricular repolarization and arrhythmogenesis. However, the importance of SK channels in human arrhythmia remains unclear. The purpose of the present study was to test the association between genetic polymorphism of the SK2 channel and the occurrence of cardiac tachyarrhythmias in humans. We enrolled 327 Han Chinese, including 72 with clinically significant ventricular tachyarrhythmias (VTa) who had a history of aborted sudden cardiac death (SCD) or unexplained syncope, 98 with a history of atrial fibrillation (AF), and 144 normal controls. We genotyped 12 representative tag single nucleotide polymorphisms (SNPs) across a 141-kb genetic region containing the KCNN2 gene; these captured the full haplotype information. The rs13184658 and rs10076582 variants of KCNN2 were associated with VTa in both the additive and dominant models (odds ratio [OR] 2.89, 95% confidence interval [CI]=1.505-5.545, P=0.001; and OR 2.55, 95% CI=1.428-4.566, P=0.002, respectively). After adjustment for potential risk factors, the association remained significant. The population attributable risks of these 2 variants of VTa were 17.3% and 10.6%, respectively. One variant (rs13184658) showed weak but significant association with AF in a dominant model (OR 1.91, CI= 1.025-3.570], P=0.042). There was a significant association between the KCNN2 variants and clinically significant VTa. These findings suggest an association between KCNN2 and VTa; it also appears that KCNN2 variants may be adjunctive markers for risk stratification in patients susceptible to SCD.

AB - Potassium calcium-activated channel subfamily N member 2 (KCNN2) encodes an integral membrane protein that forms smallconductance calcium-activated potassium (SK) channels. Recent studies in animal models show that SK channels are important in atrial and ventricular repolarization and arrhythmogenesis. However, the importance of SK channels in human arrhythmia remains unclear. The purpose of the present study was to test the association between genetic polymorphism of the SK2 channel and the occurrence of cardiac tachyarrhythmias in humans. We enrolled 327 Han Chinese, including 72 with clinically significant ventricular tachyarrhythmias (VTa) who had a history of aborted sudden cardiac death (SCD) or unexplained syncope, 98 with a history of atrial fibrillation (AF), and 144 normal controls. We genotyped 12 representative tag single nucleotide polymorphisms (SNPs) across a 141-kb genetic region containing the KCNN2 gene; these captured the full haplotype information. The rs13184658 and rs10076582 variants of KCNN2 were associated with VTa in both the additive and dominant models (odds ratio [OR] 2.89, 95% confidence interval [CI]=1.505-5.545, P=0.001; and OR 2.55, 95% CI=1.428-4.566, P=0.002, respectively). After adjustment for potential risk factors, the association remained significant. The population attributable risks of these 2 variants of VTa were 17.3% and 10.6%, respectively. One variant (rs13184658) showed weak but significant association with AF in a dominant model (OR 1.91, CI= 1.025-3.570], P=0.042). There was a significant association between the KCNN2 variants and clinically significant VTa. These findings suggest an association between KCNN2 and VTa; it also appears that KCNN2 variants may be adjunctive markers for risk stratification in patients susceptible to SCD.

KW - Association studies

KW - Genetics

KW - Heart arrest

KW - Ion channel

KW - Risk prediction

KW - Ventricular arrhythmia

UR - http://www.scopus.com/inward/record.url?scp=84980042066&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84980042066&partnerID=8YFLogxK

U2 - 10.1097/MD.0000000000004312

DO - 10.1097/MD.0000000000004312

M3 - Article

VL - 95

JO - Medicine; analytical reviews of general medicine, neurology, psychiatry, dermatology, and pediatries

JF - Medicine; analytical reviews of general medicine, neurology, psychiatry, dermatology, and pediatries

SN - 0025-7974

IS - 29

M1 - e4312

ER -