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Molecular Medicine of Inherited Arrhythmias : Clinical application of genetic analysis

遗传性心律失常的分子医学：遗传分析的临床应用

基本信息

批准号：
16209025
负责人：
HORIE Minoru
金额：
$ 32.45万
依托单位：
Shiga University of Medical Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16209025/
关键词：
long QT syndrome genetic analysis Brugada syndrome drug-induced QT prolongation CPVT ARVC mutation single nucleotide polymorphism 遺伝子多型

项目摘要

During last two decades our understanding for inherited types of arrhythmias has been advanced enormously as a result of evolutionary progress in molecular genetics and electrophysiology. Starting from the long QT syndrome (LQTS), genetic variants in genes encoding ion channels and their accessory proteins have been shown to cause a variety of hereditary disorder of heart rhythm such as Brugada syndrome, familial sick sinus syndrome, catecholeminergic polymorphic ventricular tachycardia (CPVT), and even familial atrial fibrillation. These diseases are now classified under the category as the cardiac ion channelopathy. Among them, the LQTS played a key role as the "Rosetta Stone", because a number of studies on LQTS patients unveiled major mechanisms underlying the ion channelopathy. Scince the year of 1996, we have been conducting genetic test of LOQTS-related genes in patients with hereditary arrhythmias, including LQTS, Brugada syndrome, CPVT, arrhythmogenic right ventricular cardiomyo-pathy (ARVC), and other types of arrhythmias associated with inherited heart diseases. In addition, we also examined the patients with secondary LQTS. To date, eight distinct genes responsible for LQTS have been found including those for Andersen (LQT7) and Timothy (LQT8) syndromes on chromosome ; 11q15.5 (KCNQ1 ; LQT1), 7q35-36 (KCNH2 ; LQT2), 3p21 (SCN5A ; LQT3), 4q25-27 (ANKB ; LQT4), 21q22 (KCNE1 ; LQT5), 21q22 (KCNE2 ; LQT6), 17q23 (KCNJ2 ; LQT7) and 12p13.3 (CACN1c ; LQT8). Our cohort now contains more than 300 individuals with LQTS and ~100 with other types of inherited arrhythmias. We also conducted the biophysical functional assay resultant from the mutations in candidate genes, and our results in this cohort have been published in several world-known journals as summarized below.

在过去的二十年里，由于分子遗传学和电生理学的进化进步，我们对遗传性心律失常类型的理解有了很大的进步。从长QT综合征(LQTS)开始，离子通道及其附属蛋白编码基因的遗传变异可引起多种遗传性心律失常，如Brugada综合征、家族性病态窦房结综合征、儿茶酚胺能多形性室性心动过速(CPVT)，甚至家族性心房颤动。这些疾病现在被归类为心脏离子通道病。其中，LQTS起着“罗塞塔石”的关键作用，因为许多对LQTS患者的研究揭示了离子通道病的主要机制。自1996年以来，我们一直在对遗传性心律失常患者进行LOQTS相关基因检测，包括LQTS、Brugada综合征、CPVT、致心律失常性右室心肌病(ARVC)以及其他类型的遗传性心脏病相关心律失常。此外，我们还对继发性LQTS患者进行了检查。到目前为止，已发现8个与LQTS相关的基因，包括染色体上的Andersen(LQT7)和Timothy(LQT8)综合征；11q15.5(KCNQ1；LQT1)、7q35-36(KCNH2；LQT2)、3p21(SCN5A；LQT3)、4q25-27(ANKB；LQT4)、21q22(KCNE1；LQT5)、21q22(KCNE2；LQT6)、17q23(KCNJ2；LQT7)和12p13.3(CACN1c；LQT8)。我们的队列现在有300多名LQTS患者和约100名其他类型的遗传性心律失常患者。我们还进行了候选基因突变产生的生物物理功能分析，我们在该队列中的结果已发表在几个世界知名期刊上，概述如下。

项目成果

期刊论文数量（33）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Mutation site-specific differences in arrhythmic risk and sensitivity to sympathetic stimulation in the LQT1 form of congenital long QT syndrome

先天性长 QT 综合征的 LQT1 型心律失常风险和对交感神经刺激敏感性的突变位点特异性差异

DOI：
发表时间：
2004
期刊：
J Am Coll Cardiol 44
影响因子：
0
作者：
Margolis RL;Holmes;S E.;Rosenblatt;A.;Gourley;L.;O'Hearn;E.;Ross;C A.;Seltzer;W K.;Walker;RH.;Ashizawa;T.;Rasmussen;A.;Hayden;M.;Almqvist;E W.;Harris;J.;Fahn;S.;MacDonald;M E.;Mysore;J.;Shimohata;T.;Tsuji;S.;Potter;N.;Shimizu W
通讯作者：
Shimizu W

Real-time confocal visualization of intracellular Ca dynamics of Purkinje fibers in Langendorff-perfused rat hearts.

Langendorff 灌注大鼠心脏浦肯野纤维细胞内 Ca 动力学的实时共焦可视化。