Molecular mechanisms and therapeutic targets of severe hypertriglyceridemia

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08467
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Takase Satoru 東京大学, 医学部附属病院, 助教 (80508094)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: hypertriglyceridemia / APOC2

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.

Free Research Field

糖尿病学、脂質代謝学

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。