Latent Genetic Backgrounds and Molecular Pathogenesis in Drug-Induced Long-QT Syndrome
Latent Genetic Backgrounds and Molecular Pathogenesis in Drug-Induced Long-QT Syndrome
复制标题
DOI：
10.1161/circep.109.862649
复制
发表时间：
2009-10-01
影响因子：
8.4
通讯作者：
Horie, Minoru
中科院分区：
文献类型：
--
作者：
Itoh, Hideki;Sakaguchi, Tomoko;Horie, Minoru
背景-具有 I-Kr 阻断作用的药物会导致继发性长 QT 综合征。一些病例与编码心脏离子通道的基因突变有关，但其在药物引起的长QT综合征（dLQTS）患者中的频率以及由此产生的分子效应仍不清楚。方法和结果-对20名dLQTS受试者和176名先天性长QT综合征（cLQTS）受试者中的长QT综合征相关基因进行了基因检测；使用中国仓鼠卵巢细胞异源表达系统和计算机模拟模型分析了 dLQTS 相关突变的电生理特征。 dLQTS 的阳性突变率与 cLQTS 相似（dLQTS 与 cLQTS 相比，20 名受试者中有 8 名 [40%] 对比 176 名受试者中有 91 名 [52%]，P=0.32）。由非抗心律失常药物诱发的尖端扭转型室速患者的突变发生率高于抗心律失常药物（抗心律失常药物与其他药物相比，14 名受试者中的 3 名 [21%] 与 6 名受试者中的 5 名 [83%]，P
Background-Drugs with I-Kr-blocking action cause secondary long-QT syndrome. Several cases have been associated with mutations of genes coding cardiac ion channels, but their frequency among patients affected by drug-induced long-QT syndrome (dLQTS) and the resultant molecular effects remain unknown.Methods and Results-Genetic testing was carried out for long-QT syndrome-related genes in 20 subjects with dLQTS and 176 subjects with congenital long-QT syndrome (cLQTS); electrophysiological characteristics of dLQTS-associated mutations were analyzed using a heterologous expression system with Chinese hamster ovary cells together with a computer simulation model. The positive mutation rate in dLQTS was similar to cLQTS (dLQTS versus cLQTS, 8 of 20 [40%] versus 91 of 176 [52%] subjects, P=0.32). The incidence of mutations was higher in patients with torsades de pointes induced by nonantiarrhythmic drugs than by antiarrhythmic drugs (antiarrhythmic versus others, 3 of 14 [21%] versus 5 of 6 [83%] subjects, P