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A Common Variant in SCN5A and the Risk of Ventricular Fibrillation Caused by First ST-Segment Elevation Myocardial
Reza Jabbari1, Charlotte Glinge1, Javad Jabbari1
1Heart Center, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Insights
Genetic variants in SCN5A are linked to ventricular fibrillation (VF) during ST-elevation myocardial infarction (STEMI). This study identified a specific SCN5A variant associated with increased VF risk in STEMI patients.
Area of Science:
- Cardiovascular Genetics
- Electrophysiology
- Genomics
Background:
- Common genetic variants are linked to ventricular fibrillation (VF) and sudden cardiac death (SCD).
- Replication of these genetic associations in diverse cohorts is limited.
- The role of these variants in VF during ST-elevation myocardial infarction (STEMI) requires investigation.
Purpose of the Study:
- To investigate whether common genetic variants previously associated with VF/SCD contribute to VF in patients experiencing their first STEMI.
- To analyze the association of specific single nucleotide polymorphisms (SNPs) with VF in the context of STEMI.
Main Methods:
- A case-control study (GEvami) involving 257 STEMI patients with VF (cases) and 537 STEMI patients without VF (controls) of Danish ethnicity.
- Analysis of 27 candidate SNPs previously linked to SCD/VF.
- Statistical association testing, including logistic regression adjusted for clinical factors.
Main Results:
- One SNP, rs11720524 in the SCN5A gene, showed a significant association with VF in STEMI (OR=1.87, P=0.017).
- The association remained significant after adjusting for clinical confounders (OR=1.9, P=0.032).
- A marginal association was observed for rs9388451 in the HEY2 gene.
Conclusions:
- A common intronic variant in the SCN5A gene is associated with VF during first STEMI.
- Further research into the functional impact of this noncoding SCN5A variant may elucidate mechanisms of VF predisposition in STEMI.
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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