Exploratory study to identify genetic defects of type I/V hyperlipoproteinemia using Next-Generation Sequencing

• Project/Area Number: 26860688
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• 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): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: hypertriglyceridemia / APOC2 / whole genome sequencing / 原発性脂質異常症 / whole genome sequence

Outline of Final Research Achievements

Previously we reported a case of hypoapoC-II with severe hypertriglyceridemia (HTG) phenotype without any mutation in the coding region of the APOC2 gene (Case 1). Whole genome sequencing revealed a rearrangement around the APOC2 gene. Southern blot hybridization analysis, array CGH analysis, and breakpoint analysis supported the result. Other 2 cases of severe HTG with decreased levels of plasma apoC-II proteins were also analyzed (Case 2 and Case 3). Surprisingly, Case 2 showed the same result as Case 1 by array CGH analysis and breakpoint analysis, indicating they have the same rearrangements. We further genotyped tag SNPs of these 2 patients by microarray and detected a founder haplotype. We propose a new disease entity “hypoapoC-II” that is derived from a structural abnormality around APOC2 gene and results in massive HTG.

Research Products

• [Presentation] Molecular dissection of hypoapoC-II caused by defective apoC-II mRNA transcription (2014)
  • Author(s): Satoru Takase, Hiroyuki Ishiura, Jun Mitusi, Hayato Fujita, Kazuo Hara, Mikio Takanashi, Jun-ichi Osuga, Shun Ishibashi, Shoji Tsuji, Takashi Kadowaki and Hiroaki Okazaki
  • Organizer: 9th Metabolic Syndrome, type II Diabetes and Atherosclerosis congress
  • Place of Presentation: Kyoto
  • Year and Date: 2014-09-12 – 2014-09-14
• [Presentation] 全ゲノム解析を用いたapoC-II低下症の原因遺伝子の探索 (2014)
  • Author(s): 高瀬暁、石浦浩之、三井純、藤田逸人、原一雄、高梨幹生、飯塚陽子、吉田博、大須賀淳一、石橋俊、辻省次、門脇孝、岡崎啓明
  • Organizer: 第46回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-07-10 – 2014-07-11
• [Presentation] whole genome sequence 解析を用いたapoC-II低下症の原因遺伝子変異同定の試み (2014)
  • Author(s): 高瀬暁、石浦浩之、三井純、藤田逸人、原一雄、関谷元博、五十嵐正樹、高梨幹生、泉田欣彦、久保田みどり、升田紫、平美乃、岡崎佐智子、飯塚陽子、矢作直也、大橋健、吉田博、柳内秀勝、多田紀夫、後藤田貴也、大須賀淳一、石橋俊、辻省次、門脇孝、岡崎啓明
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-05-22 – 2014-05-24