Abstract
BackgroundRecent studies suggest that variants in two calcium handling genes (RyR2 and CASQ2) associated with sudden cardiac death (SCD) and non-sudden cardiac death (NSCD) in subjects with heart failure and coronary artery disease, respectively. The purpose of this study was to identify other calcium handling genes associated with SCD in the long-term of chronic heart failure (CHF) in Chinese Han population.Methods and ResultsWe investigated 20 SNPs representing 10 genes that regulated calcium handling in 1429 patients with CHF, and the genetic association with SCD and all-cause death was analysed. During a median follow-up period of 63 months, 538 patients (37.65%) died from CHF, of whom 185 (34.38%) had SCD and the others were NSCD. SNPs that pass a P value cut-off of 0.0025 were considered as significant. We found that patients carrying the CC genotype of rs3814843 on CALM1 gene had greater risks of SCD (HR 5.542, 95% CI 2.054–14.948, P = .001) and all cause death (HR 3.484, 95% CI 1.651–7.350, P = .001). After adjusting for other risk factors, significant associations remained. Moreover, patients carrying G allele of rs361508 on TRDN gene also had increased risk of SCD.ConclusionsCommon variants in TRDN and CALM1 are associated with increased risk of SCD in patients with CHF. These findings provide further evidence for association of variants in calcium handling regulating proteins and SCD in chronic heart failure.
Highlights
Chronic Heart failure (CHF) afflicts 4 million people in China, with increased incidence and prevalence in aged subjects[1]
We investigated 20 SNPs representing 10 genes that regulated calcium handling in 1429 patients with chronic heart failure (CHF), and the genetic association with sudden cardiac death (SCD) and all-cause death was analysed
We found that patients carrying the CC genotype of rs3814843 on CALM1 gene had greater risks of SCD (HR 5.542, 95% CI 2.054–14.948, P = .001) and all cause death (HR 3.484, 95% CI 1.651–7.350, P = .001)
Summary
Chronic Heart failure (CHF) afflicts 4 million people in China, with increased incidence and prevalence in aged subjects[1]. SCD is caused by lethal ventricular arrhythmia, such as ventricular tachycardia (VT) and ventricular fibrillation (VF). Ca2+ plays crucial role in lethal arrhythmias. Function of crucial channels (LTCC, RyR2 and SERCA2) is regulated by regulatory proteins and adrenergic receptor signaling cascade, such as calsequestrin 2 (CASQ2), calmodulin (CALM1), phospholamban (PLN), protein kinase A (PRKACG), and Ca2+/calmodulin-dependent protein kinases IIδ(CAMK2D). Recent studies suggest that variants in two calcium handling genes (RyR2 and CASQ2) associated with sudden cardiac death (SCD) and non-sudden cardiac death (NSCD) in subjects with heart failure and coronary artery disease, respectively. The purpose of this study was to identify other calcium handling genes associated with SCD in the long-term of chronic heart failure (CHF) in Chinese Han population
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