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

Institut for Klinisk Medicin

10 Citationer (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.

Originalsprog	Engelsk
Artikelnummer	e0170193
Tidsskrift	PLOS ONE
Vol/bind	12
Udgave nummer	1
Antal sider	12
ISSN	1932-6203
DOI	https://doi.org/10.1371/journal.pone.0170193
Status	Udgivet - 1 jan. 2017

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10.1371/journal.pone.0170193Licens: CC BY

A Common Variant in SCN5A and the Risk of Ventricular Fibrillation Caused by First STSegment Elevation Myocardial InfarctionForlagets udgivne version, 886 KBLicens: CC BY

Citationsformater

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), [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, bind 12, nr. 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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doi = "10.1371/journal.pone.0170193",

language = "English",

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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.

KW - Aged

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

VL - 12

JO - PLoS Computational Biology

JF - PLoS Computational Biology

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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