Molecular Dissection of hypoapoC-II caused by defective mRNA transcription

2013 Fiscal Year Final Research Report

• Project/Area Number: 24790914
• 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): 2012-04-01 – 2014-03-31
• Keywords: chylomicronemia / apoC-II deficiency / SNP / rare variant

Research Abstract

Familial apolipoprotein C-II (apoC-II) deficiency is a rare autosomal recessive disorder with marked hypertriglyceridemia resulting from impaired activation of LPL. In most cases of apoC-II deficiency, causative mutations have been found in the protein-coding region of APOC2 gene; however, several atypical cases of apoC-II deficiency were reported to have markedly reduced, but detectable levels of plasma apoC-II protein (hereafter referred to as hypoapoC-II). A case of apoC-II deficiency was found that is phenotypically identical to hypoapoC-II. We took advantage of a monocyte/macrophage culture system to prove that transcription of apoC-II mRNA was decreased in the patient's cells. However, all of the fifty single nucleotide variants detected in the patient's APOC2 gene were common variants that are supposedly not causative, implying that other mutations regulate apoC-II levels. Whole-genome sequencing is underway to identify the causative mutation.

Research Products

• [Journal Article] Apolipoprotein C-II deficiency with no rare variant in the APOC2 gene (2013)
  • Author(s): Takase S, Osuga J, Fujita H, Hara K, Sekiya M, Igarashi M, Takanashi M, Takeuchi Y, Izumida Y, Ohta K, Kumagai M, Nishi M, Kubota M, Masuda Y, Taira Y, Okazaki S, Iizuka Y, Yahagi N, Ohashi K, Yoshida H, Yanai H, Tada N, Gotoda T, Ishibashi S, Kadowaki T, Okazaki H
  • Journal Title: J Atheroscler Thromb Volume: 20 (5) Pages: 481- 93
  • Peer Reviewed
• [Presentation] 蛋白翻訳領域に変異の無いapoC-II欠損/低下症の分子生物学的解析 (2013)
  • Author(s): 高瀬暁, 大須賀淳一, 藤田逸人, 原一雄, 高梨幹生, 泉田欣彦, 久保田みどり, 升田紫, 飯塚陽子, 吉田博, 柳内秀勝, 多田紀夫, 山田信博, 石橋俊, 岡崎啓明, 門脇孝
  • Organizer: 第34回日本肥満学会
  • Place of Presentation: 東京
  • Year and Date: 2013-10-12
• [Presentation] 蛋白翻訳領域に変異の無い非典型的アポC-II 欠損症の分子生物学的解析 (2013)
  • Author(s): 高瀬暁, 大須賀淳一, 藤田逸人, 原一雄, 高梨幹生, 飯塚陽子, 吉田博, 柳内秀勝, 多田紀夫, 山田信博, 石橋俊, 岡崎啓明, 門脇孝
  • Organizer: 第45回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2013-07-18
• [Presentation] Apolipoprotein C-II deficiency with no rare variant in the APOC2 gene (2013)
  • Author(s): 高瀬暁, 大須賀淳一, 藤田逸人, 原一雄, 関谷元博, 五十嵐正樹, 高梨幹生, 武内謙憲, 泉田欣彦, 太田啓介, 熊谷真義, 西真貴子, 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, 柳井秀勝, 多田紀夫, 後藤田貴也, 石橋俊, 岡崎啓明, 門脇孝
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
  • Year and Date: 2013-05-16