Genetic background of inherited cardiac arrhythmias

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461054
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Kyoto University
• Principal Investigator: Makiyama Takeru 京都大学, 医学(系)研究科(研究院), 助教 (30528302)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 臨床心臓学 / 不整脈 / イオンチャネル

Outline of Final Research Achievements

This study aimed to elucidate the phenotype-genotype relationship in the inherited arrhythmias and reveal the underlying mechanisms, especially, using a newly developed technology, ’patient specific induced pluripotent stem (iPS) cell model’. We identified a cardiac sodium channel mutation in a patient with sinus node dysfunction and epinephrine-induced QT prolongation. The electrophysiological properties of the mutant channels were closely associated with the overlapping clinical features of the patient. Regarding the disease-specific iPS model, we generated CPVT-iPS cell model and recapitulated arrhythmogenic features which were suppressed by a promising compound, S107. In addition, we established long QT syndrome-iPS model associated with an L-type Ca channel gene mutation and identified the impaired inactivation in the mutant channels. In LMNA-related cardiomyopathy, we investigated the impact of the type of mutation to the development of decreased left ventricular function.

Free Research Field

臨床心臓学