Establishment of precision medicine for cardiomyopathy using genome analysis and single cell analysis

2018 Fiscal Year Final Research Report

• Project/Area Number: 17H06566
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Cardiovascular medicine
• Research Institution: Chiba University
• Principal Investigator: Satoh Masahiro 千葉大学, 医学部附属病院, 医員 (10802564)
• Project Period (FY): 2017-08-25 – 2019-03-31
• Keywords: 循環器内科学 / 精密医療

Outline of Final Research Achievements

In this study, we performed targeted sequencing on dilated cardiomyopathy and hypertrophic cardiomyopathy in Japan. Dilated cardiomyopathy patients harboring TTN truncating variants had better prognosis than those with LMNA variants. Most patients with TTN truncating variants achieved left ventricular reverse remodeling, unlike most patients with LMNA variants. We performed single cardiomyocyte RNA sequencing and single molecule fluorescence in situ hybridization and elucidated heart failure patients with a high proportion of failing cardiomyocytes have treatment resistance. To achieve the mechanism about the whole heart tissue of cardiomyopathy patients, we are integrating the genome analysis and single cell analysis.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

現在心筋症の治療法は心不全や致死性不整脈などの臨床症状のみに依存する形で画一的に選択されている。しかし、本研究により治療反応性の予測可能な遺伝子変異を同定することに成功し、さらに1細胞解析をヒトサンプルに応用することにも成功した。予後を含めた詳細な臨床情報、心筋症ゲノム解析、single cell RNA sequencing, 心筋生検を用いた1分子RNAI FISHなどの1細胞解析を統合し心筋症予後予測確立へむけて解析を進めている。