A Common Variant in SCN5A and the Risk of Ventricular Fibrillation Caused by First ST-Segment Elevation Myocardial Infarction

Reza Jabbari; Charlotte Glinge; Javad Jabbari; Bjarke Risgaard; Bo Gregers Winkel; Christian Juhl Terkelsen; Hans-Henrik Tilsted; Lisette Okkels Jensen; Mikkel Hougaard; Stig Haunsø; Thomas Engstrøm; Christine M Albert; Jacob Tfelt-Hansen

doi:10.1371/journal.pone.0170193

A Common Variant in SCN5A and the Risk of Ventricular Fibrillation Caused by First ST-Segment Elevation Myocardial Infarction

Reza Jabbari, Charlotte Glinge, Javad Jabbari, Bjarke Risgaard, Bo Gregers Winkel, Christian Juhl Terkelsen, Hans-Henrik Tilsted, Lisette Okkels Jensen, Mikkel Hougaard, Stig Haunsø, Thomas Engstrøm, Christine M Albert, Jacob Tfelt-Hansen

Department of Clinical Medicine

10 Citations (Scopus)

74 Downloads (Pure)

Abstract

BACKGROUND: Several common genetic variants have been associated with either ventricular fibrillation (VF) or sudden cardiac death (SCD). However, replication efforts have been limited. Therefore, we aimed to analyze whether such variants may contribute to VF caused by first ST-elevation myocardial infarction (STEMI).

METHODS: We analyzed 27 single nucleotide polymorphisms (SNP) previously associated with SCD/VF in other cohorts, and examined whether these SNPs were associated with VF caused by first STEMI in the GEnetic causes of Ventricular Arrhythmias in patients with first ST-elevation Myocardial Infarction (GEVAMI) study on ethnical Danes. The GEVAMI study is a prospective case-control study involving 257 cases (STEMI with VF) and 537 controls (STEMI without VF).

RESULTS: Of the 27 candidate SNPs, one SNP (rs11720524) located in intron 1 of SCN5A which was previously associated with SCD was significantly associated with VF caused by first STEMI. The major C-allele of rs11720524 was present in 64% of the cases and the C/C genotype was significantly associated with VF with an odds ratio (OR) of 1.87 (95% CI: 1.12-3.12; P = 0.017). After controlling for clinical differences between cases and controls such as age, sex, family history of sudden death, alcohol consumption, previous atrial fibrillation, statin use, angina, culprit artery, and thrombolysis in myocardial infarction (TIMI) flow, the C/C genotype of rs11720524 was still significantly associated with VF with an OR of 1.9 (95% CI: 1.05-3.43; P = 0.032). Marginal associations with VF were also found for rs9388451 in HEY2 gene. The CC genotype showed an insignificant risk for VF with OR = 1.50 (95% CI: 0.96-2.40; P = 0.070).

CONCLUSION: One common intronic variant in SCN5A suggested an association with VF caused by first STEMI. Further studies into the functional abnormalities associated with the noncoding variant in SCN5A may lead to important insights into predisposition to VF during STEMI.

Original language	English
Article number	e0170193
Journal	PLOS ONE
Volume	12
Issue number	1
Number of pages	12
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0170193
Publication status	Published - 1 Jan 2017

Keywords

Aged
Case-Control Studies
Denmark
Female
Genotype
Humans
Male
Middle Aged
Myocardial Infarction
NAV1.5 Voltage-Gated Sodium Channel
Polymorphism, Single Nucleotide
Ventricular Fibrillation
Journal Article

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A Common Variant in SCN5A and the Risk of Ventricular Fibrillation Caused by First STSegment Elevation Myocardial InfarctionFinal published version, 886 KBLicence: CC BY

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Jabbari, R., Glinge, C., Jabbari, J., Risgaard, B., Winkel, B. G., Terkelsen, C. J., Tilsted, H.-H., Jensen, L. O., Hougaard, M., Haunsø, S., Engstrøm, T., Albert, C. M., & Tfelt-Hansen, J. (2017). A Common Variant in SCN5A and the Risk of Ventricular Fibrillation Caused by First ST-Segment Elevation Myocardial Infarction. PLOS ONE, 12(1), Article e0170193. https://doi.org/10.1371/journal.pone.0170193

Jabbari, R, Glinge, C, Jabbari, J, Risgaard, B, Winkel, BG, Terkelsen, CJ, Tilsted, H-H, Jensen, LO, Hougaard, M, Haunsø, S, Engstrøm, T, Albert, CM & Tfelt-Hansen, J 2017, 'A Common Variant in SCN5A and the Risk of Ventricular Fibrillation Caused by First ST-Segment Elevation Myocardial Infarction', PLOS ONE, vol. 12, no. 1, e0170193. https://doi.org/10.1371/journal.pone.0170193

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title = "A Common Variant in SCN5A and the Risk of Ventricular Fibrillation Caused by First ST-Segment Elevation Myocardial Infarction",

abstract = "BACKGROUND: Several common genetic variants have been associated with either ventricular fibrillation (VF) or sudden cardiac death (SCD). However, replication efforts have been limited. Therefore, we aimed to analyze whether such variants may contribute to VF caused by first ST-elevation myocardial infarction (STEMI).METHODS: We analyzed 27 single nucleotide polymorphisms (SNP) previously associated with SCD/VF in other cohorts, and examined whether these SNPs were associated with VF caused by first STEMI in the GEnetic causes of Ventricular Arrhythmias in patients with first ST-elevation Myocardial Infarction (GEVAMI) study on ethnical Danes. The GEVAMI study is a prospective case-control study involving 257 cases (STEMI with VF) and 537 controls (STEMI without VF).RESULTS: Of the 27 candidate SNPs, one SNP (rs11720524) located in intron 1 of SCN5A which was previously associated with SCD was significantly associated with VF caused by first STEMI. The major C-allele of rs11720524 was present in 64% of the cases and the C/C genotype was significantly associated with VF with an odds ratio (OR) of 1.87 (95% CI: 1.12-3.12; P = 0.017). After controlling for clinical differences between cases and controls such as age, sex, family history of sudden death, alcohol consumption, previous atrial fibrillation, statin use, angina, culprit artery, and thrombolysis in myocardial infarction (TIMI) flow, the C/C genotype of rs11720524 was still significantly associated with VF with an OR of 1.9 (95% CI: 1.05-3.43; P = 0.032). Marginal associations with VF were also found for rs9388451 in HEY2 gene. The CC genotype showed an insignificant risk for VF with OR = 1.50 (95% CI: 0.96-2.40; P = 0.070).CONCLUSION: One common intronic variant in SCN5A suggested an association with VF caused by first STEMI. Further studies into the functional abnormalities associated with the noncoding variant in SCN5A may lead to important insights into predisposition to VF during STEMI.",

keywords = "Aged, Case-Control Studies, Denmark, Female, Genotype, Humans, Male, Middle Aged, Myocardial Infarction, NAV1.5 Voltage-Gated Sodium Channel, Polymorphism, Single Nucleotide, Ventricular Fibrillation, Journal Article",

author = "Reza Jabbari and Charlotte Glinge and Javad Jabbari and Bjarke Risgaard and Winkel, {Bo Gregers} and Terkelsen, {Christian Juhl} and Hans-Henrik Tilsted and Jensen, {Lisette Okkels} and Mikkel Hougaard and Stig Hauns{\o} and Thomas Engstr{\o}m and Albert, {Christine M} and Jacob Tfelt-Hansen",

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T1 - A Common Variant in SCN5A and the Risk of Ventricular Fibrillation Caused by First ST-Segment Elevation Myocardial Infarction

AU - Jabbari, Reza

AU - Glinge, Charlotte

AU - Jabbari, Javad

AU - Risgaard, Bjarke

AU - Winkel, Bo Gregers

AU - Terkelsen, Christian Juhl

AU - Tilsted, Hans-Henrik

AU - Jensen, Lisette Okkels

AU - Hougaard, Mikkel

AU - Haunsø, Stig

AU - Engstrøm, Thomas

AU - Albert, Christine M

AU - Tfelt-Hansen, Jacob

PY - 2017/1/1

Y1 - 2017/1/1

N2 - BACKGROUND: Several common genetic variants have been associated with either ventricular fibrillation (VF) or sudden cardiac death (SCD). However, replication efforts have been limited. Therefore, we aimed to analyze whether such variants may contribute to VF caused by first ST-elevation myocardial infarction (STEMI).METHODS: We analyzed 27 single nucleotide polymorphisms (SNP) previously associated with SCD/VF in other cohorts, and examined whether these SNPs were associated with VF caused by first STEMI in the GEnetic causes of Ventricular Arrhythmias in patients with first ST-elevation Myocardial Infarction (GEVAMI) study on ethnical Danes. The GEVAMI study is a prospective case-control study involving 257 cases (STEMI with VF) and 537 controls (STEMI without VF).RESULTS: Of the 27 candidate SNPs, one SNP (rs11720524) located in intron 1 of SCN5A which was previously associated with SCD was significantly associated with VF caused by first STEMI. The major C-allele of rs11720524 was present in 64% of the cases and the C/C genotype was significantly associated with VF with an odds ratio (OR) of 1.87 (95% CI: 1.12-3.12; P = 0.017). After controlling for clinical differences between cases and controls such as age, sex, family history of sudden death, alcohol consumption, previous atrial fibrillation, statin use, angina, culprit artery, and thrombolysis in myocardial infarction (TIMI) flow, the C/C genotype of rs11720524 was still significantly associated with VF with an OR of 1.9 (95% CI: 1.05-3.43; P = 0.032). Marginal associations with VF were also found for rs9388451 in HEY2 gene. The CC genotype showed an insignificant risk for VF with OR = 1.50 (95% CI: 0.96-2.40; P = 0.070).CONCLUSION: One common intronic variant in SCN5A suggested an association with VF caused by first STEMI. Further studies into the functional abnormalities associated with the noncoding variant in SCN5A may lead to important insights into predisposition to VF during STEMI.

AB - BACKGROUND: Several common genetic variants have been associated with either ventricular fibrillation (VF) or sudden cardiac death (SCD). However, replication efforts have been limited. Therefore, we aimed to analyze whether such variants may contribute to VF caused by first ST-elevation myocardial infarction (STEMI).METHODS: We analyzed 27 single nucleotide polymorphisms (SNP) previously associated with SCD/VF in other cohorts, and examined whether these SNPs were associated with VF caused by first STEMI in the GEnetic causes of Ventricular Arrhythmias in patients with first ST-elevation Myocardial Infarction (GEVAMI) study on ethnical Danes. The GEVAMI study is a prospective case-control study involving 257 cases (STEMI with VF) and 537 controls (STEMI without VF).RESULTS: Of the 27 candidate SNPs, one SNP (rs11720524) located in intron 1 of SCN5A which was previously associated with SCD was significantly associated with VF caused by first STEMI. The major C-allele of rs11720524 was present in 64% of the cases and the C/C genotype was significantly associated with VF with an odds ratio (OR) of 1.87 (95% CI: 1.12-3.12; P = 0.017). After controlling for clinical differences between cases and controls such as age, sex, family history of sudden death, alcohol consumption, previous atrial fibrillation, statin use, angina, culprit artery, and thrombolysis in myocardial infarction (TIMI) flow, the C/C genotype of rs11720524 was still significantly associated with VF with an OR of 1.9 (95% CI: 1.05-3.43; P = 0.032). Marginal associations with VF were also found for rs9388451 in HEY2 gene. The CC genotype showed an insignificant risk for VF with OR = 1.50 (95% CI: 0.96-2.40; P = 0.070).CONCLUSION: One common intronic variant in SCN5A suggested an association with VF caused by first STEMI. Further studies into the functional abnormalities associated with the noncoding variant in SCN5A may lead to important insights into predisposition to VF during STEMI.

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KW - Case-Control Studies

KW - Denmark

KW - Female

KW - Genotype

KW - Humans

KW - Male

KW - Middle Aged

KW - Myocardial Infarction

KW - NAV1.5 Voltage-Gated Sodium Channel

KW - Polymorphism, Single Nucleotide

KW - Ventricular Fibrillation

KW - Journal Article

U2 - 10.1371/journal.pone.0170193

DO - 10.1371/journal.pone.0170193

M3 - Journal article

C2 - 28085969

SN - 1932-6203

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JO - PLOS ONE

JF - PLOS ONE

IS - 1

M1 - e0170193

ER -

A Common Variant in SCN5A and the Risk of Ventricular Fibrillation Caused by First ST-Segment Elevation Myocardial Infarction

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