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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.

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