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

Abstract

BackgroundSeveral 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).MethodsWe 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).ResultsOf 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).ConclusionOne 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.

Single nucleotide polymorphisms of SCN5A and SCN10A genes increase the risk of ventricular arrhythmias during myocardial infarction

“…Our results are in agreement with a case-control study that found no association between 24 common genetic variants, including rs2200733, related to AF and the risk of VF in the setting of first STEMI. 40 Our results support the idea that cardiac electrical abnormalities may be the result of variations in genes coding ion channels. On the other hand, our study shows that SNPs in genes involved in embryonic cardiogenesis, previously associated with congenital heart rhythm diseases, are not associated with acquired heart rhythm disorders.…”

Modifier genes for sudden cardiac death

“…One SNP located in intron 1 of SCN5A (rs11720524) showed an association with arrhythmic risk. 64 However, when the field moved from candidate genes to GWAS, none of the SNPs or the genes previously associated with lifethreatening arrhythmias in different clinical settings and during AMI showed a significant signal. Two GWAS reported an association of common genetic variants with VF/SCD at a genome-wide statistical significance (P < 5 Â 10 -8 ).…”

Association study of new polymorphisms with sudden cardiac death in men

“…В первой части исследования были изучены полиморфизмы трех генов GNB3, GNAQ, GNAS в отношении ассоциа-лено, что ассоциация полиморфизма с ВСС более выражена в группе больных с ИБС [15]. Известно, что полиморфизм rs11720524 гена ассоциирован с фибрилляцией желудочков [16]. Ген SCN5A (sodium voltage-gated channel alpha subunit 5, 3p22.2) кодирует α-субъединицу натриевого канала.…”