Common RyR2 variants associate with ventricular arrhythmias and sudden cardiac death in chronic heart failure

Ca2+ cycling plays a critical role in heart failure and lethal arrhythmias. As susceptibility to sudden cardiac death is considered to be a heritable trait in general population, we have therefore investigated whether potentially functional variants of genes encoding RyR2 (ryanodine receptor 2) and the L-type Ca2+ channel are related to the risk of ventricular arrhythmias and sudden cardiac death in CHF (chronic heart failure) in a case-control study. We found that the A allele of rs3766871 in RYR2 was associated with an increased risk of ventricular arrhythmias in patients with CHF odds ratio, 1. 66 95% CI (confidence interval), 1. 21-2. 26; P=0. 002. During a median follow-up period of 32 months in 1058 (85. 0%) patients, 296 (28. 0%) patients died from heart failure, of whom 141 (47. 6%) had sudden cardiac death. After adjustment for age, gender and suspected risk factors, patients carrying the A allele of rs3766871 had an increased risk of cardiac death HR (hazard ratio), 1. 53 95% CI, 1. 11-2. 12; P=0. 010 and sudden cardiac death HR, 1. 92 (95% CI, 1. 25-2. 94) ; P=0. 003. Patients carrying the A allele of rs790896 in RYR2 had a reduced risk of sudden cardiac death HR, 0. 65 (95% CI, 0. 45-0. 92) ; P=0. 015. In conclusion, the A allele of rs3766871 in RYR2 not only associates with ventricular arrhythmias, but also serves as an independent predictor of sudden cardiac death, and the A allele of rs790896 in RYR2 is a protective factor against sudden cardiac death in patients with CHF.