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2007 Fiscal Year Final Research Report Summary

Functional dissection of a polymorphism in TLR2 gene associated with liver fibrosis in chronic hepatitis C

Research Project

Project/Area Number 18590715
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionYamagata University

Principal Investigator

LI Shao  Yamagata University, Dept. of Public Health, Assistant Professor (80344787)

Co-Investigator(Kenkyū-buntansha) SAITO Takahumi  Yamagata University, Dept. of Gastroenterology, Assistant Professor (80250918)
KAWATA Sumio  Yamagata University, Dept. of Gastroenterology, Professor (90183285)
FUKAO Akira  Yamagata University, Dept. of Public Health, Professor (80156736)
Project Period (FY) 2006 – 2007
KeywordsHepatitis C / Innate immune / TLR2 / Single nucleotide polymorphism / HCV replicon
Research Abstract

The progression of liver fibrosis in chronic hepatitis C is influenced by both genetic and environmental factors although its detailed mechanism has not been unraveled yet. Inflammation and activation of hepatic stellate cell are thought to be the principal effectors of hepatic fibrogenesis. Recent studies suggested that toll-like receptor 2 (TLR2), an innate immune sensor, plays an important role in the inflammation response triggered by HCV core and NS3 proteins. To investigate whether functional polymorphisms across the TLR2-related genes affect the liver fibrosis progression, a genetic association study was conducted in patients with chronic hepatitis C. The results showed that a deletion polymorphism in TLR2 gene is significantly associated with liver fibrosis progression. We hypothesized that this variant in TLR2 gene affects the liver fibrosis by altering the expression of inflammation cytokines or influencing the HCV replication in hepatocytes. To test the hypothesis, we transfected TLR2-siRNA into HCV replicon cell lines Huh7.5 that stably produce infectious virions. Silencing of TLR2 expression had no significant effect on HCV replication. We further assessed the difference in inflammatory cytokine expression in monocytes between individuals with deletion-type and wild-type TLR2. Monocytes from the deletion-type-TLR2-individuals produced more IL-6 in response to stimulation with HCV. This finding supported the possibility that the polymorphism in TLR2 affects the cytokine expression and activity, consequently influencing the liver fibrosis progression in chronic hepatitis C.

  • Research Products

    (8 results)

All 2007 2006

All Journal Article (4 results) Presentation (4 results)

  • [Journal Article] Functional polymorphisms in the toll-like receptor 2 gene and liver fibrosis in chronic hepatitis C2007

    • Author(s)
      Shao, L・Ishii, K・Saito, T, et. al.
    • Journal Title

      Hepatol Inter 1

      Pages: 139

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Functional polymorphisms in the Toll-Like receptor 2 gene and liver fibrosis in chronic hepatitis C2007

    • Author(s)
      Shao L, Ishii K, Saito T, Watanabe H, Sugahara K, Nishise Y, Okumoto K, Ishii R, Kawata S, Ishikawa H, Fukao A
    • Journal Title

      Hepatol Inter 1

      Pages: 139

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Association of transforming growth factor-beta 1 functional polymorphisms with natural clearance of hepatitis C virus2006

    • Author(s)
      Kimura, T・Saito, T・Kawat, S, et. al.
    • Journal Title

      J Infect Dis 10

      Pages: 1371-1374

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Association of transforming growth factor-beta 1 functional polymorphisiiis with natural clearance of hepatitis C virus2006

    • Author(s)
      Kimura T, Saito T, Yoshimura M, Yixuan S, Baba M, JiG, Muramatsu M, Kawata S.
    • Journal Title

      J Infect Dis 193

      Pages: 1371-1374

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Hyperprolactinemia associated with chronic hepatitis C and induction of prolactin expression in human peripheral blood mononuclear cells stimulated by hepatitis C virus2007

    • Author(s)
      Ishii R, Saito T, Shao L, Ugajin S, Sato C, Haga H, Suzuki A, Misawa K, Sanjo M, Nishise Y, Okumoto K, Ito J, Sugahara K, Saito K, Togashi H, Kawata S
    • Organizer
      58th AASLD
    • Place of Presentation
      Boston, USA
    • Year and Date
      20071100
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Functional polymorphisms in the Toll-Like receptor 2 gene and liver fibrosis in chronic hepatitis C2007

    • Author(s)
      Shao L, Ishii K, Saito T, Watanabe H, Sugahara K, Nishise Y, Okumoto K, Ishii R, Kawata S, Ishikawa H, Fukao A
    • Organizer
      17th APASL
    • Place of Presentation
      Kyoto
    • Year and Date
      20070300
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] TLR2扇面遺伝子群の遺伝子多型とC型慢性肝炎の病態との関連についての解析2007

    • Author(s)
      邵 力・石井健一・齋藤貴史, など
    • Organizer
      第43回日本肝臓学会総会
    • Place of Presentation
      東京
    • Year and Date
      2007-06-01
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] ハブロタイプ分析を用いたCHUK, IKBKB 遺伝子と肝線維化進展との関連の検討2007

    • Author(s)
      石井健一・邵 力・齋藤貴史, など
    • Organizer
      第17回日本疫学会
    • Place of Presentation
      広島
    • Year and Date
      2007-01-27
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2010-02-04  

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