RyR2常见基因变异:心力衰竭致猝死的遗传学预测因子  

Common RyR2 Variant:A Genetic Predictor of Sudden Cardiac Death in chronic Heart Failure

作　　者：张洪亮[1] 冉玉琴[1] 陈敬洲[1] 柳志红[1] 浦介麟[1] 

机构地区：[1]北京协和医学院中国医学科学院国家心血管病中心阜外医院,北京市100037

出　　处：《中国分子心脏病学杂志》2017年第1期1983-1987,共5页Molecular Cardiology of China

基　　金：973国家基础研究发展计划项目(2007CB512000);(2007CB512008)

摘　　要：目的研究表明心源性猝死是一种可遗传的性状,本研究将探索心肌细胞钙释放通道RyR2具有潜在功能的基因变异与室性心律失常和心源性猝死的相关性。方法从2005年7月至2008年1月,入选就诊于阜外医院的冠心病或扩张型心肌病导致的慢性心力衰竭患者,匹配年龄性别相近的对照。门诊和电话随访患者死亡和猝死终点。候选基因分析RYR2的2个基因变异rs41315858(G1885E)、rs3766871(G1886S),连接酶反应技术和基因测序进行基因分型,结合临床资料和随访结果使用Logistic回归、Cox回归模型和生存分析方法对2个候选基因变异进行关联研究。结果共入选1244例心力衰竭患者和1032例对照,其中676例(54.3%)心力衰竭患者伴有室性心律失常。基因分析显示rs3766871 A等位基因携带与心力衰竭患者发生室性心律失常的风险增加相关(OR=1.66,95%CI:1.21-2.26,P=0.002)。中位随访32个月,校正年龄、性别和可能相关的危险因素后,rs3766871A等位基因携带者心源性死亡(HR=1.53,95%CI:1.11-2.12,P=0.01)和心源性猝死的风险增加(HR=1.92,95%CI:1.25-2.94,P=0.003)。结论 RYR2上的基因变异rs3766871 A等位基因携带不仅增加慢性力衰患者室性心律失常的风险,而且是心源性猝死的遗传学预测因子。Objective Studies showed that susceptibility to sudden cardiac death was a heritable trait in general population. We investigated whether potentially functional variants of RyR2 were related to the risk of ventricular arrhythmias and sudden cardiac death in patients with chronic heart failure. Methods From July 2005 to January 2008, consecutive patients with chronic heart failure resulted from coronary heart disease and idiopathic dilated cardiomyopathy referred to Fu Wai Hospital were recruited. Controls were matched with similar gender and age. Participants were genotyped using ligase detection reactions for two variants, rs41315858 （G1885E） and rs3766871 （G 1886S） in RYR2. Multivariate logistic regression, Cox proportional-hazards models and survival analysis were used for statistical analysis. Results A total of 1244 chronic heart failure patients and 1032 control subjects were enrolled. Genotyping revealed that the A allele of rs3766871 in RYR2 was associated with increased risk of ventricular arrhythmias in heart failure patients （OR=1.66, 95% CI=1.21-2.26; P=0.002）. During a median follow-up for 32 months, patients carrying the A allele of rs3766871 had an increased risk for cardiac death （HR=1.53, 95% CI=1. 11-2.12; P=0.01） and sudden cardiac death （HR=1.92, 95% CI=1.25-2.94; P=0.003） after adjusted age, gender and suspected risk factors. Conclusions The A allele of rs3766871 in RYR2 not only associates with ventricular arrhythmias but also serves as an independent predictor of sudden cardiac death in chronic heart failure patients.

关 键 词：心力衰竭 心源性猝死 室性心律失常 钙释放通道 遗传变异 

分 类 号：R541.6[医药卫生—心血管疾病]