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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。
Aims Studies have shown that sudden cardiac death is a heritable trait. In this study, we will explore the relationship between the potential gene mutation of RyR2 and the occurrence of ventricular arrhythmia and sudden cardiac death in cardiomyocytes. Methods From July 2005 to January 2008, patients with CHD caused by coronary heart disease or dilated cardiomyopathy who were referred to Fu Wai Hospital were enrolled and matched with similar age and sex. Outpatient and telephone follow-up of patients with death and sudden death. Candidate genes were genotyped for the two genetic variations of RYR2 rs41315858 (G1885E), rs3766871 (G1886S), ligase reaction and gene sequencing. Logistic regression, Cox regression model and survival analysis were used to analyze the clinical data and follow-up results. Candidate genetic variations were correlated. Results A total of 1244 patients with heart failure and 1032 controls were enrolled. Among them, 676 (54.3%) patients with heart failure had ventricular arrhythmias. Genetic analysis showed that the rs3766871 A allele was associated with an increased risk of developing ventricular arrhythmias in patients with heart failure (OR = 1.66, 95% CI: 1.21-2.26, P = 0.002). After a median follow-up of 32 months, the association of rs3766871A allele with cardiac death (HR = 1.53, 95% CI: 1.11-2.12, P = 0.01) and cardiogenic The risk of sudden death increased (HR = 1.92, 95% CI: 1.25-2.94, P = 0.003). CONCLUSION: The genetic variation of rs3766871 A allele on RYR2 not only increases the risk of ventricular arrhythmia in patients with chronic heart failure, but also is a genetic predictor of sudden cardiac death.