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ANALYSIS OF IMMUNOGENETIC BACKGROUNDS OF PRIMARY BILIARY CIRRHOSIS IN JAPAN

Research Project

Project/Area Number 05670485
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionKOCHI MEDICAL SCHOOL

Principal Investigator

MAEDA Takashi  FIRST DEPARTMENT OF INTERNAL MEDICINE,Kochi Medical School, ASSISTANT PROFESSOR, 医学部, 助手 (80183606)

Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1993: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsPRIMARY BILIARY CIRRHOSIS / HLA CLASS II / TAP2 / TNFalpha GENE / HLA / TNFα遺伝子 / TAP
Research Abstract

With respect to immunogenetic backgrounds, the association of primary biliary cirrhosis (PBC) with major histocompatibility complex (MHC) antigens has been controversial. Recently, a strong association of PBC with HLA DR8 has been reported in Caucasians and Japanese. Furthermore, an association between PBC and immunoregulatory alleles including TNFalpha, C4B2, and B-associated transcript, which are located in the vicinity of the MHC genes, has been also reported in Caucasians. We investigated MHC genes and its vicinity in Japanese PBC,including HLA DRB1, B3, B4, B5, DQA1 and B1, TNFalpha, gamma and transporter associated with antigen processing (TAP2).
[Methods] Genotypes of HLA DRB,DQA,and DQB were determined by PCR-SSOP method. Polymorphism of TNFalpha was investigated by restriction fragment length polymorphism (RFLP) with Ncol. The Ile * Val substitution at position 379 in the transmembrane domain of TAP2 was determined by PCR-SSO analysis.
[Results] (1) Gene frequency of the DRB1^*0 … More 803 was significantly increased in patients with PBC (gf : 35.5%, relative risk : 6.84, p<0.0001). DRB1^*0803 showed, however, no association with any clinical or laboratory findings includings histological stages, major symptoms (jaundice and/or pruritus), and AMA titers. DQA1^*0103 and DQB1^*0601 were also increased in PBC due to strong linkage disequilibrium with DRB1^*0803 on the same haplotype. In contrast, DQA1^*0102 was significantly less frequent (p<0.05). (2) Differing from the published observation from Danish PBC,the significant decreased frequency of the 10.5kb Ncol fragment of TNFalpha was not found in Japnaese PBC.(3) No significant differences in the amino acid substitution of TAP2 were not observed between PBC and normal controls.
[Conclusions] HLA DRB1^*0803 itself may be the primary gene responsible for predisposition to PBC among Japanese individuals. In the context of antigen presentation and recognition through HLA class II antigens, identification of target antigens on biliary epithelial cells and analysis of cellular interaction through DRB1^*0803 will be important. Less

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Takashi Maeda: "The association of primary biliary cirrhosis with HLA DRw8 in Japan" Int Hepatol Commun. 1. 104-108 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Saburo Onishi: "DNA typing of HLA class II genes; DRB1^*0803 increases the susceptibility of Japanese to primary biliary cirrhosis" J Hepatol. 21. 1053-1060 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takako Miyamoto: "T cell autoreactivity against a 28kD biliary protein(B1-p28) in primary biliary cirrhosis" J Hepatol. 22(in press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 前田 隆: "医学のあゆみ 原発性胆汁性肝硬変(PBC)-最近のトピックス" 医歯薬出版, 468 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 前田 隆: "消化器病セミナー54 原発性胆汁性肝硬変:病態・治療・予後" へるす出版, 181 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takashi Maeda et al.: "The association of primary biliary cirrhosis with HLA DRw8 in Japan." Int Hepatol Commun.1. 104-108 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Saburo Onishi et al.: "DNA typing of HLA class II genes ; DRB1^*0803 increases the susceptibility of Japanese to primary biliary cirrhosis." J Hepatol. 21. 1053-1060 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takako Miyamoto et al.: "T cell autoreactivity against a 28 kD biliary protein (B1-p28) in primary biliary cirrhosis." J Hepatol. 22(in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Saburo Onishi: "DNA typing of HLA class II genes;DRB1^*0803 increases the susceptibility of Japanese primary biliary cirrhasis" Journal of Hepatology. 21. 1053-1060 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 前田隆: "消化器病セミナー54 原発性胆汁性肝硬変・病態・治療・予後" へるす出版, 181 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takashi Maeda: "The association of primary bilialy cirrhosis with HLA DRw8 in Japan21GC01:International Hepatology Communications" 1. 104-108 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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