| Project/Area Number |
01480192
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | Medical Institute of Bioregulation, Kyushu University |
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Principal Investigator |
KIMURA Akinori Department of Genetics, Medical Institute of Bioregulation, Kyushu University, Research Associate, 生体防御医学研究所, 助手 (60161551)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIMURA Yasuharu Department of Genetics, Medical Institute of Bioregulation, Kyushu University, A, 生体防御医学研究所, 助教授 (10156119)
SASAZUKI Takehiko Department of Genetics, Medical Institute of Bioregulation, Kyushu University, P, 生体防御医学研究所, 教授 (50014121)
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| Project Period (FY) |
1989 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1991: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1990: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1989: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | HLA / Polymorphisms / Promoter region / Expression / Transcription factor / 発現調節 / TNF / IFN / トランスジェニックマウス / DNAタイピング / 自己免疫疾患 / HLAクラスII遺伝子 / 転写調節 / サイトカイン / 核蛋白 |
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| Research Abstract |
To decipher the molecular mechanism of the association between HLA and autoinsune diseases, we have investigated the polymorphisms of HLA class I and class 11 genes in the coding and promoter regions. The highly polymorphic second exons of HLA-B. DRB1. DRBS, DRB4. DRB5. DRB6. DQA1. DQB1. DPAI. and DPBI genes were analyzed by the PCR-SSOP and PCR-SSCP methods. and 27, 51, 3.1.4.3.9.14.8. and 36 alleles. respectively. were defined. In addition, cytoplasmic exons of HLA-DRA and DQBL genes were found to be polymorphic, as well 9 allelic differences in the promoter region of the DQAL gene were identified. These polymorphisms were analysed in healthy individuals antipatients with several autoimmune diseases including IDDM. RA, Graves' disease. Behcet's disease, Takayasu arteritis, Hashim to hyroiditis. SLE. mixed connective tissue disease, and specific alleles were identified to be strongly associated with each disease. Moreover, the regulation of the HLA class 11 genes, especially their inductions by cytokinesis such as interferons and TNFs were investigated in detail. and it was found that the HLA-DQAL gene was differently regulated from the other class 11 genes by means of expressivity and inducibility via a DQAL gene-specific positive transcription factor NF-TRS. The binding sites of NF-TRS is overlapping with that of another transcription factor NF-Y and the polymorphism at the sites was found to affect the binding affinity for these factors. suggesting that the expression of the HLA-DQAL gene is allele-specific and may play a role in immune regulation and in developing the autoimmune diseases.
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