Abstract

BackgroundCohort studies have revealed an increased risk for ventricular fibrillation (VF) and sudden cardiac death (SCD) in patients with atrial fibrillation (AF). In this study, we hypothesized that single nucleotide polymorphisms (SNP) previously associated with AF may be associated with the risk of VF caused by first ST-segment elevation myocardial infarction (STEMI).MethodsWe investigated association of 24 AF-associated SNPs with VF in the prospectively assembled case–control study among first STEMI-patients of Danish ancestry.ResultsWe included 257 cases (STEMI with VF) and 537 controls (STEMI without VF). The median age at index infarction was 60 years for the cases and 61 years for the controls (p = 0.100). Compared to the control group, the case group was more likely to be male (86% vs. 75%, p = 0.001), have a history of AF (7% vs. 2%, p = 0.006) or hypercholesterolemia (39% vs. 31%, p = 0.023), and a family history of sudden death (40% vs. 25%, p < 0.001). All 24 selected SNPs have previously been associated with AF. None of the 24 SNPs were associated with the risk of VF after adjustment for age and sex under additive genetic model of inheritance in the logistic regression model.ConclusionIn this study, we found that the 24 AF-associated SNPs may not be involved in increasing the risk of VF. Larger VF cohorts and use of new next generation sequencing and epigenetic may in future identify additional AF and VF risk loci and improve our understanding of genetic pathways behind the two arrhythmias.

Highlights

  • Cohort studies have revealed an increased risk for ventricular fibrillation (VF) and sudden cardiac death (SCD) in patients with atrial fibrillation (AF)

  • In the Danish GEVAMI (GEnetic causes of Ventricular Arrhythmias in patients with first ST-elevation Myocardial Infarction) study we have previously demonstrated a strong association between AF and VF before

  • We hypothesized single nucleotide polymorphisms (SNP) that previously were associated with AF can affect the risk of VF in the GEVAMI study population and thereby suggest a shared genetic pathway

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Summary

Introduction

Cohort studies have revealed an increased risk for ventricular fibrillation (VF) and sudden cardiac death (SCD) in patients with atrial fibrillation (AF). We hypothesized that single nucleotide polymorphisms (SNP) previously associated with AF may be associated with the risk of VF caused by first ST-segment elevation myocardial infarction (STEMI). In the Danish GEVAMI (GEnetic causes of Ventricular Arrhythmias in patients with first ST-elevation Myocardial Infarction) study we have previously demonstrated a strong association between AF and VF before. Single nucleotide polymorphisms (SNP) on Jabbari et al BMC Medical Genetics (2017) 18:138 chromosomes 4q25 (PITX2) have strong association with AF [9, 14], and with higher risk of SCD [15]. We hypothesized SNPs that previously were associated with AF can affect the risk of VF in the GEVAMI study population and thereby suggest a shared genetic pathway SCN5A and SCN10A which encode the transient sodium channel (INa) and play a pivotal role in membrane depolarization during cardiac action potentials have been associated with AF, [16, 17] VF [17], and Brugada Syndrome [18, 19].

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