Analysis of the genetic backgrounds of familial hypercholesterolemia to achieve the effective therapy.

2009 Fiscal Year Final Research Report

• Project/Area Number: 20790642
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Metabolomics
• Research Institution: Kanazawa University
• Principal Investigator: NOGUCHI Tohru Kanazawa University, 医学系研究科, 特任助教 (40456421)
• Project Period (FY): 2008 – 2009
• Keywords: 家族性高コレステロール血症 / LDL受容体 / MLPA法 / apo-B-100 / PCSK9 / インベーダーアッセイ法 / 遺伝子大規模欠失・重複変異

Research Abstract

In this study, we introduced the multiplex ligation-dependent probe amplification (MLPA) to detect copy number variations (CNVs) of the low-density lipoprotein receptor gene in 518 familial hypercholesterolemia (FH) subjects. As the result of this research, 8 CNVs were newly identified and the mutation detection rate was improved from 63.5% to 73.0%. Furthermore, we revealed the effects of the proprotein convertase subtilisin/kexin type 9 gene mutations on the clinical phenotype of FH.

Research Products

• [Journal Article] The E32K variant of PCSK9 exacerbates the phenotype of familial hypercholesterolaemia by increasing PCSK9 function and concentration in the circulation (2010)
  • Author(s): Noguchi, T., Katsuda, S., Kawashiri, MA., T ada, H., Nohara, A., Inazu, A., Yamagishi, M., Kobayashi, J., Mabuchi, H.
  • Journal Title: Atherosclerosis 210 Pages: 166-172
  • Peer Reviewed
• [Presentation] Common E32K mutation in the PCSK9 gene exacerbates the phenotype of familial hypercholesterolaemia despite moderate increase in plasma PCSK9 and LDL-C levels per se (2010)
  • Author(s): Noguchi, T.
  • Organizer: CSK9 Conference
  • Place of Presentation: Chambre de commerce et d'industrie de Nantes (France)
  • Year and Date: 2010-03-11
• [Presentation] Effects of PCSK9 E32K and LDLR mutations on circulating PCSK9 levels (2009)
  • Author(s): 野口徹
  • Organizer: 第41回日本動脈硬化学会総会
  • Place of Presentation: 海峡メッセ下関(山口県)
  • Year and Date: 2009-07-17
• [Presentation] Profiles of gain-of-function PCSK9 E32K mutation: including pure homozygote and compound heterozygote with LDLR gene mutation (2009)
  • Author(s): Noguchi, T.
  • Organizer: XV International Symposium on Atherosclerosis
  • Place of Presentation: John B. Hynes Convention Center (USA)
  • Year and Date: 2009-06-16
• [Presentation] PCSK9遺伝子E32K変異と家族性高コレステロール血症 (2008)
  • Author(s): 野口徹
  • Organizer: 第40回日本動脈硬化学会総会
  • Place of Presentation: つくば国際会議場(茨城県)
  • Year and Date: 2008-07-11