Molecular mechanisms and therapeutic targets of severe hypertriglyceridemia
| Project/Area Number |
18K08467
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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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| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Takase Satoru 東京大学, 医学部附属病院, 助教 (80508094)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | hypertriglyceridemia / APOC2 / 脂質異常症 / リポ蛋白 / リポタンパク / MTTP / 高カイロミクロン血症 / 無βリポ蛋白血症 |
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| Outline of Final Research Achievements |
Previously we reported a case of hypoapoC-II with severe hypertriglyceridemia without any mutation in the coding region of the APOC2 gene. Whole genome sequencing revealed a rearrangement around the APOC2 gene. Southern blot hybridization analysis, array CGH analysis, and breakpoint analysis supported the result. Because same results were also shown in another case and a founder haplotype was detected by SNP genotyping of these patients, we proposed that the “hypoapoC-II” was derived from a structural abnormality around APOC2 gene. It is supposed partial tandem duplication of APOC2 gene including proximal promoter region may cause transcriptional defects of the gene.
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| Academic Significance and Societal Importance of the Research Achievements |
著明な高中性脂肪血症は頻回に急性膵炎を合併するため、社会生活が著しく妨げられる。従来の内服加療のみでは有効な改善は得難く、毎日の極めて厳しい食事制限が必須となるため生涯に渡りQOL低下が甚だしい。hypoapoC-IIモデルマウス構築により詳細な病態解明、急性膵炎発症機序解明、更には新規治療法の開発に帰着できれば、患者QOLの向上が望める。また、本疾患構造変異による転写減少のメカニズムを解明できれば、他疾患の解釈にも応用できる可能性が期待される。
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Report
(4 results)
Research Products
(2 results)
