Abstract 19099: Genome-Wide Association Study Identifies a Region at Chr 21q21 as a Susceptibility Locus for Ventricular Fibrillation in Acute Myocardial Infarction
Sudden cardiac death is a leading mode of death in adults in the Western world. The largest proportion of these deaths is caused by ventricular fibrillation (VF) during acute myocardial infarction (MI). The identification of genetic variants associated with this phenotype is challenging due to difficulties in ascertaining these patients. We report here the first genome-wide association study addressing this problem. Genome-wide association analysis in a discovery set of 972 patients with a first acute MI, 515 of whom had VF and 457 did not, identified 8 SNPs, all at chromosome 21q21 and in moderate to complete linkage disequilibrium (LD) with each other, associated with VF. Of these, the most significant association was found for rs2824292 and rs2824293 within 338bp of each other and in complete LD (O.R.=1.78; 95% CI, 1.47-2.13; P=3.3×10−10). The association of rs2824292 with VF was then replicated in an independent case-control set consisting of 146 out-of-hospital cardiac arrest patients with MI and VF and 391 MI survivor controls (O.R.=1.49; 95% CI, 1.14-1.95; P=0.004). The gene closest to rs2824292 is CXADR, which encodes a viral receptor implicated in myocarditis and dilated cardiomyopathy, and which has recently been identified as a modulator of cardiac conduction. This locus has not previously been implicated in arrhythmia susceptibility.
- © 2010 by American Heart Association, Inc.