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

2015 Fiscal Year Final Research Report

• 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
• Keywords: hypertriglyceridemia / APOC2 / whole genome sequencing

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.

Free Research Field

糖尿病学、脂質代謝学