Clinical Impact of Genetic Studies in Lethal Inherited Cardiac Arrhythmias
Clinical Impact of Genetic Studies in Lethal Inherited Cardiac Arrhythmias
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DOI：
10.1253/circj.cj-08-0947
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发表时间：
2008-12-01
影响因子：
3.3
通讯作者：
Shimizu, Wataru
中科院分区：
文献类型：
--
作者：
Shimizu, Wataru
在过去的十年中，分子遗传学研究已经确定了许多遗传性心律失常（包括先天性长QT综合征（LQTS）和Brugada综合征（BrS））与编码离子通道或其他膜成分的基因突变之间的联系。在50-70%的临床受累患者中发现了12种LQTS。LQT 1、LQT 2和LQT 3综合征的基因型-表型相关性已得到严格研究，这些综合征占基因型LQTS患者的90%以上，从而能够对基因型患者进行风险分层和有效治疗。基因型特异性触发心脏事件和临床过程已被报道，基因型特异性治疗已被引入。最近，在LQT 1和LQT 2患者中报告了临床表型的突变位点特异性差异，表明突变位点特异性管理或治疗的可能性。相反。只有三分之一的BrS患者可以进行基因分型，并且临床研究中基因型-表型关系的数据有限。最近仅在亚洲人中发现了由SCN 5A基因近端启动子区域内的6个个体DNA多态性组成的单倍型B（频率22%）。具有单倍型B的个体显示PQ和QRS的持续时间显著长于不具有单倍型B的个体，表明单倍型B可能导致亚洲人群中BrS的较高发病率。(Circ J 2008; 72：1926-1936）
Over the past decade, molecular genetic studies have established a link between a number of inherited cardiac arrhythmias, including congenital long QT syndrome (LQTS) and Brugada syndrome (BrS), and mutations in genes encoding for ion channels or other membrane components. Twelve forms of LQTS have been identified in 50-70% of clinically affected patients. Genotype-phenotype correlations have been rigorously investigated in LQT1, LQT2 and LQT3 syndromes, which constitute more than 90% of genotyped LQTS patients, enabling stratification of risk and effective treatment of genotyped patients. Genotype-specific triggers for both the cardiac events and the clinical course have been reported, and genotype-specific therapy has been already introduced. More recently, Mutation site-specific differences in the clinical phenotype have been reported in LQT1 and LQT2 patients, indicating the possibility of mutation site-specific management or treatment. In contrast. only one-third of BrS patients can be genotyped, and data on genotype-phenotype relationships in clinical studies are limited. A Haplotype B consisting of 6 individual DNA polymrphisms within the proximal promoter region of he SCN5A gene was recently identified only in Asians (frequency 22%). Individuals with Haplotype B show significantly longer duration of both PQ and QRS than those without Haplotype B, indicating that Haplotype B likely contributes to the higher incidence of BrS in Asian populations. (Circ J 2008; 72: 1926-1936)