| Project/Area Number |
02404082
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | Osaka University |
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Principal Investigator |
KONO Norio (1991) Osaka Univ Med Sch, 2nd Dpt Int Med, Associate Prof., 医学部, 助教授 (30093412)
垂井 清一郎 (1990) 大阪大学, 医学部, 教授 (00028341)
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| Co-Investigator(Kenkyū-buntansha) |
宮川 潤一郎 大阪大学, 医学部附属病院, 医員
NAMBA Mitsuyoshi Osaka Univ Med Sch, 2nd Dpt Int Med, Assistant Prof., 医学部, 助手 (00183533)
HANAFUSA Toshiaki Osaka Univ Med Sch, 2nd Dpt Int Med, Assistant Prof., 医学部, 助手 (60164886)
KUWAJIMA Masamichi Osaka Univ Med Sch, 2nd Dpt Int Med, Assistant Prof., 医学部, 講師 (00205262)
MIYAGAWA Jun-ichiro Osaka Univ Hospital, 2nd Dpt Int Med, Senior Resident.
川知 雅典 大阪大学, 医学部附属病院, 医員
朝川 秀樹 大阪大学, 医学部附属病院, 医員
河野 典夫 大阪大学, 医学部, 講師 (30093412)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥12,800,000 (Direct Cost: ¥12,800,000)
Fiscal Year 1991: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1990: ¥8,800,000 (Direct Cost: ¥8,800,000)
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| Keywords | Type 1 diabetes / HLA-DQ / HLA-DR / HLA-DP / TNF / Molecular Biology / Genetics / Autoimmunity / HLAーDR抗原 / HLAーDQ抗原 / PCR / 病因遺伝子 / RFLP |
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| Research Abstract |
Type I (insulin-dependent) diabetes mellitus results from the autoimmune-mediated destruction of pancreatic fl-cells. Genetic backgrounds are important in the pathogenesis of the disease, and candidates for susceptible genes are HLA antigen genes. To clarify the susceptible genes for Type I diabetes, we studied genes of HLA class 11 (DQ, DR and DP) antigen as well as those of TNF (tumor necrosis factor) on the same chromosome 6.
DNA were obtained from lymphocytes of Japanese IDDM patients and healthy control subjects. We analyzed HLA class II and TNF genes using a combination of polymerase chain reaction (PCR) and either dot blot hybridization with allele specific oligonucleotide probes or restriction fragment length polymorphism (RFLP) analysis.
The results showed that 1) DQA1*1 contributes to resistance and DQAI*3 confers susceptibility to Type I diabetes, 2) aspartic acid at position 57 of DQ A does not necessarily protect against Type I diabetes in Japanese subjects, 3) DQwl. 2 contributes to resistance both in Japanese and in Caucasians, 4) HLA- DR alone is not sufficient for the development of Type I diabetes, and 5) neither HLA-DP nor TNF gene is associated with Type I diabetes.
These results indicate the importance of DQAL and DQBL genes in the development of Type I diabetes. Particularly in Japanese subjects, DQA1*1 and DQwl. 2 contribute to resistance and DQAI*3 confers susceptibility to Type I diabetes.
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