Department of Internal Medicine, Cardiovascular Medicine/Cardiac Electrophysiology, American University of Beirut Faculty of Medicine, Beirut, Lebanon.
Department of Physiologic Nursing; Institute for Human Genetics.
Heart Rhythm. 2014 Apr;11(4):646-52. doi: 10.1016/j.hrthm.2014.01.015. Epub 2014 Jan 17.
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).
The purpose of this study was to examine the association of common CASQ2 SNPs with the risk of SCA in patients with CAD.
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.
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, 95% CI 13.40-52.70, P <.001) led us to further examine the relationship between CHF, SCA, and CASQ2 SNPs. We identified 2 CASQ2 variants (rs7521023: OR 0.4, 95% CI 0.25-0.76, P = .003; rs6684209: OR 19.8, 95% CI 3.63-108.2, P <.001) associated with CHF after adjusting for SCA, age, gender, and hypertension.
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.
异常钙处理在心律失常、心脏性猝死（SCA）和充血性心力衰竭（CHF）中起着关键作用。钙结合蛋白 2（CASQ2）突变会影响钙释放，并引发恶性室性心律失常（VA）和 SCA 综合征。CASQ2 常见的单核苷酸多态性（SNP）可能与冠心病（CAD）患者的 SCA 相关。
本研究旨在探讨常见 CASQ2 SNP 与 CAD 患者 SCA 风险的相关性。
在一项病例对照研究中，对 114 例因 VA 导致的 CAD 和 SCA 患者与 311 例无 VA 或 SCA 的 CAD 对照组进行了 CASQ2 SNP（n = 14）的基因分型和分析。
多变量 logistic 回归分析调整年龄和 CHF 状态后，发现 rs7521023 与 SCA 相关（比值比 [OR] 2.72，95%置信区间 [CI] 1.44-5.13，P =.002）。模型中 CHF 对 SCA 的显著影响（OR 26.6，95% CI 13.40-52.70，P <.001）促使我们进一步研究 CHF、SCA 和 CASQ2 SNP 之间的关系。我们发现了 2 个 CASQ2 变异（rs7521023：OR 0.4，95% CI 0.25-0.76，P =.003；rs6684209：OR 19.8，95% CI 3.63-108.2，P <.001）与调整 SCA、年龄、性别和高血压后 CHF 相关。
我们观察到 CAD 患者因 VA 导致的 SCA 与 CASQ2 多态性相关，在调整 CHF 后，CASQ2 SNP 与 CHF 相关，在调整 SCA 后。需要在独立队列中进一步研究以证实这些发现。
