心律失常的分子遗传学进展:从基因到疾病的诊断和治疗  

Advances in molecular genetics of cardiac arrhythmias:from genes to patients

作　　者：王擎[1,2] 张贤钦[1] 任翔[1] 

机构地区：[1]华中科技大学人类基因组研究中心 [2]Department of Biological,Geological,and Environmental Science,Cleveland State University,Cleveland,OH 44115,USA

出　　处：《中华心律失常学杂志》2004年第6期350-359,共10页Chinese Journal of Cardiac Arrhythmias

基　　金：科技部 863重大专项研究资助 (2 0 0 2BA711A0 7) ;美国NIH资助 (HL65 63 0 ;HL662 5 1;HL73 817) ;AHAEstablishedInvestigatoraward项目

摘　　要：心律失常是影响公众健康的一种重要病症 ,是常见的致死原因。分子遗传学在过去十年的重要进展 ,为我们理解心律失常的发病机理提供了很大帮助。 5 0 %～ 75 %的长QT综合征 (LQTS)和 15 %～ 35 %Brugada综合征 (BS)的致病基因已经被发现 (LQTS :钾通道基因KCNQ1,KCNH2 ,KCNE1,KCNE2 ,KCNJ2 ;钠通道基因SCN5A ;非离子通道基因ankyrin B。BS :SCN5A)。遗传性LQTS致病基因的突变也与很多普通药物诱导的LQTS相关。基因特异性治疗和遗传诊断已经应用于LQTS和Brugada综合征。最近发现一种新的短QT综合征与KCNQ1和KCNH2突变有关。心脏钠离子通道基因SCN5A的突变也可导致心脏传导疾病和常染色体隐性病态窦房结综合征 (SSS)。散发型SSS也与心脏起搏钾离子通道基因HCN4的突变有关。心脏ryanodinereceptor 2基因 (RYR2 )和calsequestrin2基因 (CASQ2 )的突变能导致儿茶酚胺多形室性心动过速。KCNQ1和KCNE2的突变可导致心房颤动。蛋白激酶基因PRKAG2是预激综合征 (Wolff Parkinson Whitesyndrome,WPWS)的致病基因。心律失常方面的已有研究成果与发现和将来的遗传学发现将会对疾病的治疗乃至现代医学产生革命性的影响。这些范例使现代医学向着个体针对性治疗发生转变 ,并首先在LQTS的治疗方面实现了 。Cardiac arrhythmias are a major public health problem and a common cause of morbidity and mortality.Significant advances from molecular genetic studies in the past decade have provided remarkable insights into the pathogenic mechanisms of cardiac arrhythmias.Pathogenic genes have been identified for 50%～75% of cases of long QT syndrome (LQTS,potassium channel genes KCNQ1,KCNH2,KCNE1,KCNE2,KCNJ2;sodium channel gene SCN5A;non-ion channel gene ankyrin-B) and 15%～35% cases of Brugada syndrome (BS,SCN5A).Mutations in genes for inherited LQTS are also associated with much more common drug-induced LQTS.Gene-specific therapy and genetic testing are now available for LQTS and Brugada syndrome(BS).A new short QT syndrome (SQTS) has been identified and found to be linked to unique mutations in KCNQ1 and KCNH2.Mutations in the cardiac sodium channel gene SCN5A also cause cardiac conduction disease and autosomal recessive sick sinus syndrome (SSS).Sporadic SSS is associated with mutations in the cardiac pace-maker potassium channel gene HCN4.The cardiac ryanodine receptor 2 gene (RYR2) and the calsequestrin 2 gene (CASQ2) cause catecholaminergic polymorphic ventricular tachycardia.Mutations in KCNQ1 and KCNE2 are linked to atrial fibrillation.A protein kinase gene PRKAG2 has been identified for Wolff-Parkinson-White syndrome.These and future genetic findings in cardiac arrhythmias will have a tremendous impact on patient management,and promises to revolutionize the modern medicine.The paradigm shift of modern medicine to “the right medicine/therapy for the right patient”is already realized in LQTS,and will spread to other arrhythmic disorders in the future.

关 键 词：心律失常 LQTS 致病基因 突变 KCNQ1 SCN5A 治疗 分子遗传学 疾病 KCNH2 

分 类 号：R541.7[医药卫生—心血管疾病]