| Project/Area Number |
12557047
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
内科学一般
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TSUCHIYA Naoyuki Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (60231437)
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| Co-Investigator(Kenkyū-buntansha) |
KOTAKE Shigeru Tokyo Women's Medical University, Institute of Rheumatology, Lecturer, 附属膠原病リウマチ痛風センター, 講師 (00234774)
OHASHI Jun Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (80301141)
TOKUNAGA Katsushi Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (40163977)
MATSUSHITA Masaki Wakunaga Pharmaceutical Co. Ltd. Institute or Medical Research, Researcher, 創薬研究所, 研究員
OKA Takanori Wakunaga Pharmaceutical Co. Ltd. Institute for Medical Research, Laboratory Manager (Researcher), 創薬研究所, 室長(研究職)
北條 浩彦 東京大学, 大学院・医学系研究科, 助手 (60238722)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥12,400,000 (Direct Cost: ¥12,400,000)
Fiscal Year 2002: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥5,800,000 (Direct Cost: ¥5,800,000)
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| Keywords | TNFα promoter / polymorphism / haplotype / rheumatoid arihritis / Crohn's disease / myositis / narcolepsy / malaria / 前向き研究 / 間質性肺炎 / 帯状疱疹後神経痛 / TNFα / プロモータ / 全身性エリテマトーデス / 伝達不平衡テスト / 関連研究 / EMSA / プロモーター / 慢性関節リクマチ / 疾患感受性 |
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| Research Abstract |
1. We established a raipid method to determine haplotypes formed by three recently described SNPs at-1031, -863 and -857, as well as by two previously described SNPs at -308 and -238, of TNFα. Using such a system, we demonstrated that five major haplotypes could account for most of the TNFα promoter haplotypes among the population, and tentatively designated them as TNFA-U01.1, U01.2, U02, U03 and U04.
2. Increase in the hapoltype frequency of TNFA-U02 was observed in rheumatoid arthritis (RA); however, that was demonstrated to derive from the linkage disequilibrium with HLA-DRB1^*0405, A prospective study to examine the association with the severity of RA was initiated by a follow-up study of early RA patients. At 12 months after enrollment the patients carrying TNFA-U02 haplotype but not HLA-DRB1 shared epitope were found to be associated with slow progression of joint destruction and good response to treatment Further follow-up considered to be necessary.
3. Association of TNFA-U03 and HLA-DRB1^*0405 or 0410 with Crohn's disease was detected. This association was independent from each other. Among patients with polymyositis/dermatoyositis, TNFA-U03 haplotype was significantly increased in those associated with interstitial pneumonitis.
4. Among the patients with mild, severe non-cerebral and cerebral malaria. TNFA-U04 haplotype was significantly increased in cerebral malaria.
5. Association of TNF-857T, Independent from HLA-DRB1^*1501-DQB1^*0602 haplotype, was observed in narcolepsy.
6. No association with TNF haplotype was observed in systemic lupus erythematosus, microscopic polyangiitis and post-herpetic neuralgia.
7. Higher binding with the transcription factor Oct-1 was observed for TNF-863A and -857T alleles.
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