| Project/Area Number |
17K08684
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Human genetics
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| Research Institution | Tokai University (2019)
Keio University (2018)
Tokyo Medical and Dental University (2017) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
木村 彰方 東京医科歯科大学, 特命副学長 (60161551)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 心筋症 / 原因遺伝子解析 / ゲノム創薬 / 原因遺伝子 / 遺伝子解析 / 遺伝子変異 |
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| Outline of Final Research Achievements |
We investigated the etiology of cardiomyopathy and developed a new therapy. (1) The protein encoding the new causative gene X of hypertrophic cardiomyopathy (HCM) suppressed the hypertrophy of cultured cardiomyocytes induced by some compounds, and cardiac hypertrophy was induced in cultured cardiomyocytes having the X gene mutation, but it was suppressed by the X administration. We will continue to develop therapy using X. (2) Pediatric HCM and restrictive cardiomyopathy were found to carry cardiomyopathy-associated mutations at a high rate, with or without a family history, most of the mutations were identified in the sarcomere gene. (3) HCM with mid-ventricular obstruction was a high-incidence adverse event subtype in which patients carried a relatively low frequency of disease-associated gene mutations in the gene encoding sarcomere, but a relatively high frequency of disease-associated genes in dilated cardiomyopathy, suggesting a different etiology from usual type of HCM.
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| Academic Significance and Societal Importance of the Research Achievements |
若年性心臓突然死の代表疾患である肥大型心筋症(HCM)の遺伝子解析により同定した新規の原因遺伝子Xをコードする蛋白は、新規の肥大抑制因子であることが示され、今後Xを用いた新たな治療開発を進めることとする。また、小児HCMでは、成人HCMとは異なり家族歴が明らかでなくとも、原因変異が判明すること、さらに、予後が悪い心室中部閉塞型HCMは通常のHCMとは異なる原因遺伝子の変異を有していることが多いことも判明し、予防的側面から遺伝子解析が貢献する可能性がある。新たな予防、治療開発へ向けて意義のある成果である。
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