心脏钠通道SCN5A基因R1193Q(RQ)变异在多个心律失常猝死家系中报道，包括遗传性和药物性长QT综合征、Brugada综合征、进展性心脏传导障碍等。欧美人RQ变异罕见属突变，中国汉人RQ等位基因频率约6-7%，为多态性（SNP），携带者达数千万。部分RQ携带者表现心电图异常甚至心源性猝死，明确影响其表型的因素及其机制，对RQ携带者临床处理具有重要意义。钠通道功能是决定SCN5A相关疾病临床表型的分子基础，我们认为其他SCN5A基因SNP，启动子区SNP以及钠通道阻滞剂（SCB），可通过调控RQ功能影响RQ携带者临床表型。本课题以"中国心律失常注册研究"社区人群调查电子化心电图数据和血样库为基础，从分子流行病学和基础实验两个层面展开,明确RQ变异与国人心电图指标的关系、影响因素和分子机理；并探讨RQ变异对SCB敏感性的影响。本课题将为汉人RQ携带者危险评估以及SCB个体化用药提供依据。

SCN5A gene encodes the cardiac sodium channel.R1193Q (RQ) variant has been reported in a number of inherited arrhythmia syndrome, including genetic and drug-induced long QT syndrome, Brugada syndrome, progressive cardiac conduction disorders etc. It is rare and recognized as a mutation in Europeans and Americans; while the allele frequency is about 6-7% in Chinese Han, so it is a single nucleotide polymorphism (SNP). Minority of RQ carriers present abnormal ECG, even sudden death. Elucidation of underlying mechanism modulating RQ phenotype has important implications for clinical management of RQ carriers. Biophysical features of SCN5A channel are the most critical determinants for the clinical phenotypes. We propose that other SNPs in SCN5A gene, SNPs in the promoter region of SCN5A , and sodium channel blockers (SCB) can modify the RQ channel function and alter the clinical phenotypes. Based on the electronic ECG and blood samples of "China arrhythmia registry", we plan to elucidate the relationship between RQ and ECG parameters and its underlying mechanisms; furthermore we will explore the sensitivity of RQ channel to SCB. This project will provide a scientific basis for risk assessment of RQ carriers and the personalized administration of SCB in Chinese RQ carriers.