家族性长QT综合征有症状患者的遗传病因与β-肾上腺素能阻滞剂反应的相关性。

Correlation of genetic etiology with response to beta-adrenergic blockade among symptomatic patients with familial long-QT syndrome.

作者信息

Itoh T, Kikuchi K, Odagawa Y, Takata S, Yano K, Okada S, Haneda N, Ogawa S, Nakano O, Kawahara Y, Kasai H, Nakayama T, Fukutomi T, Sakurada H, Shimizu A, Yazaki Y, Nagai R, Nakamura Y, Tanaka T

机构信息

Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Japan.

出版信息

J Hum Genet. 2001;46(1):38-40. doi: 10.1007/s100380170123.

DOI:10.1007/s100380170123

PMID:11289718

Abstract

Mutations in any of the five genes KCNQ1, KCNH2, KCNE1, KCNE2, and SCN5A can be responsible for familial long QT syndrome (LQTS), an arrhythmogenic disorder that entails a high risk of sudden death. beta-Adrenergic blocking agents are the first therapeutic choice, and 80% of patients treated with these agents show symptomatic relief; however the remaining 20% do not respond well. We previously performed a nationwide analysis of familial long QT syndrome (LQTS) in Japan and identified 32 mutations in the KCNQ1 and KCNH2 genes. In the present retrospective study, we found that patients carrying mutations in the KCNQ1 gene responded better to beta-adrenergic blocking agents than those with KCNH2 mutations (12 of 13 vs 1 of 5; P = 0.0077, Fisher's exact test). This is a good example of the power of genetic diagnosis to direct the selection of appropriate therapy for patients with diseases of heterogeneous genetic etiology.

摘要

KCNQ1、KCNH2、KCNE1、KCNE2和SCN5A这五个基因中的任何一个发生突变，都可能导致家族性长QT综合征（LQTS），这是一种有致心律失常风险的疾病，会带来很高的猝死风险。β-肾上腺素能阻滞剂是首选治疗药物，80%接受这些药物治疗的患者症状得到缓解；然而，其余20%的患者反应不佳。我们之前在日本对家族性长QT综合征（LQTS）进行了全国性分析，在KCNQ1和KCNH2基因中鉴定出32个突变。在本回顾性研究中，我们发现携带KCNQ1基因突变的患者对β-肾上腺素能阻滞剂的反应比携带KCNH2基因突变的患者更好（13例中的12例 vs 5例中的1例；P = 0.0077，Fisher精确检验）。这是一个很好的例子，说明了基因诊断在指导为具有异质性遗传病因疾病的患者选择合适治疗方法方面的作用。