Abstract 14239: Testing of Genetic Variants Influencing Heart Rate and Electrocardiographic Indices of Conduction and Repolarization for Modulation of Risk of Acute Ischemia-Related Ventricular Fibrillation
Background: Sudden cardiac death is a leading mode of death in adults in the Western world. A large proportion of these deaths are caused by ventricular fibrillation (VF) during acute myocardial ischemia-infarction (MI). While a genetic component in determination of risk for VF in MI is recognized, the underlying genetic factors remain largely unknown. ECG parameters have been shown to be associated with risk of sudden death and recent genome-wide association studies (GWAS) have revealed common single nucleotide polymorphisms (SNPs) associated with variation in heart rate and ECG indices of conduction and repolarization. In this study we investigated the effect of these SNPs in modulation of VF risk in acute MI.
Methods: Patients studied were Dutch Caucasian patients with a first acute MI, with those suffering VF classified as cases (n=515) and those not suffering VF classified as controls (n=457). SNPs associated with heart rate and ECG conduction and repolarization indices at genome-wide significant p-values (P<5×10-8) in previous GWAS were identified. Genotypes for these SNPs were obtained either by direct genotyping (Illumina610) or were imputed using HapMap build 36. Logistic regression was used to test for association with VF.
Results: Besides the previously reported rs6795970 in SCN10A (A-allele OR: 0.78, 95%CI: 0.65-0.94, P=0.01), another two SNPs, rs11897119 (C-allele OR: 1.23, 95%CI: 1.03-1.49, P=0.02), and rs17779747 (T-allele OR: 1.28, 95%CI: 1.05-1.54, p=0.01) were found to influence risk of VF during MI. These effects were independent of each other. rs11897119 is located in MEIS1 and the C-allele, which increases risk of VF in this study, was previously shown to be associated with increased PR-interval in the general population. rs17779747 is located 600 kb far from KCNJ2, and the T-allele, associated with increased risk of VF in this analysis, was previously associated with shorter QT-interval in the general population.
Conclusions: SNPs previously shown to impact cardiac conduction and repolarization may modulate risk of VF during acute MI.
- © 2010 by American Heart Association, Inc.