Association of CASQ2 polymorphisms with sudden cardiac arrest and heart failure in patients with coronary artery disease

作者：Refaat Marwan M; Aouizerat Bradley E; Pullinger Clive R; Malloy Mary; Kane John; Tseng Zian H^*

来源：Heart Rhythm, 2014, 11(4): 646-652.

DOI：10.1016/j.hrthm.2014.01.015

• Sudden cardiac arrest
• Ventricular arrhythmias
• Ventricular tachycardia
• Coronary artery disease
• Congestive heart failure
• Calsequestrin 2
• Genetics

BACKGROUND Abnormal calcium handling plays a crucial role in arrhythmias, sudden cardiac arrest (SCA), and congestive heart failure (CHF). Calsequestrin 2 (CASQ2) mutations affect calcium release and initiate malignant ventricular arrhythmias (VAs) and SCA syndromes. Common single nucleotide polymorphisms (SNPs) in CASQ2 may be associated with SCA in patients with coronary artery disease (CAD). %26lt;br%26gt;OBJECTIVE The purpose of this study was to examine the association of common CASQ2 SNPs with the risk of SCA in patients with CAD. %26lt;br%26gt;METHODS CASQ2 SNPs (n = 14) were genotyped and analyzed in a case control study comparing 114 patients with CAD and SCA due to VA to 311 CAD controls without VA or SCA. %26lt;br%26gt;RESULTS Multivariate logistic regression adjusting for age and CHF status identified an association between rs7521023 with SCA (odds ratio [OR] 2.72, 95% confidence interval [CI] 1.44-5.13, P = .002). The substantial impact of CHF on SCA in the model (OR 26.6, 950/0 CI 13.40-52.70, P %26lt; .001) led us to further examine the relationship between CHF, SCA, and CASQ2 SNPs. We identified 2 CASQ2 variants (rs7521023: OR 0.4, 950/0 CI 0.25-0.76, P = .003; rs6684209: OR 19.8, 950/a CI 3.63-108.2, P %26lt; .001) associated with CHF after adjusting for SCA, age, gender, and hypertension. %26lt;br%26gt;CONCLUSION We observed association between a CASQ2 polymorphism and SCA due to VA in patients with CAD adjusting for CHF and independent associations between CASQ2 SNPs and CHF adjusting for SCA. Further investigation in independent cohorts is needed to confirm these findings.

• 出版日期2014-4