| Project/Area Number |
12307038
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | HOKKAIDO UNIVERSITY (2001)
Yokohama City University (2000) |
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Principal Investigator |
OHNO Shigeaki Hokkaido UNIV., Grad. school of Med., Prof., 大学院・医学研究科, 教授 (50002382)
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| Co-Investigator(Kenkyū-buntansha) |
KOTAKE Satoshi Hokkaido UNIV., Univ. Hospital, Lecurer, 医学部・附属病院, 講師 (00186694)
KIMURA Minoru Tokai UNIV., School of Med., Prof., 医学部, 教授 (10146706)
INOKO Hidetoshi Tokai UNIV., School of Med., Prof., 医学部, 教授 (10101932)
CHIN Sinki Hokkaido UNIV., Univ. Hospital, Instractor, 医学部・附属病院, 助手 (90236844)
YOSHIDA Kazuhiko Hokkaido UNIV., Univ. Hospital, Instractor, 医学部・附属病院, 助手 (90281807)
中村 聡 横浜市立大学, 医学部, 講師 (00237398)
伊藤 典彦 横浜市立大学, 医学部, 助手 (80264654)
内尾 英一 横浜市立大学, 医学部・附属市民総合医療センター, 助教授 (70232840)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥41,810,000 (Direct Cost: ¥37,400,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2001: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2000: ¥22,700,000 (Direct Cost: ¥22,700,000)
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| Keywords | Behcet's disease / HLA-B51 / MICA^★009 / microsatellite / immune-mediate infammatory diseases / molecular genetics / Vogt-Koyanagagi-Harada's disease / Uveitis / ヒトゲノムプロジェクト / 疾患感受性 / HLA / MICA / HLA-B51トランスジェニックマウス |
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| Research Abstract |
Intractable immune-mediate inflammatory diseases of the eye including Behcet's disease and Vogt-Koyanagagi-Harada's disease are strongly associated with HLA on the onset. First, we determined whole base sequences of HLA-class I region (1.9x10^6bp) to investigate the exact gene structure of HLA region. As a result utilizing the microsatellites in the region, we found 758 microsatellites which composed of 2-5 repeated bases. Furthermore, we performed the etiological gene mapping of Behcet's disease with 10 microsatellites of HLA class I region in the following ethnics; Japanese, Greece, Iranian, Italian, Saudi Arabian, Turkish and Chinese. Consequently, the etiological gene was successly been be narrowed down to 46kb region between MICA and HLA-B. In addition, we reported that the etiological gene of Behcet's disease exists nearby HLA-B gene. Especially HLA-B51 seems to have a significant correlation with Behcet's disease. We then compared the base sequences of HLA-B51 and its promoter region between the patients and the healthy controls. As a result, there were some single nucleotide polymorphisms (SNPs) in the intron and promoter regions; however there was no specific SNPs found in Behcet's disease. Therefore, the SNPs which characterize HLA-B51 in common may work for the responsible genetic mechanism of Behcet's disease. Moreover, we examined MICA allele frequencies in Turkish patients with Behcet's disease. As a result, MICA^★009 allele was significantly elevated in the patients group compared with the healthy controls. (R. R. = 7.1 p = 0.000046) Therefore, it was suggested that MICA^★009- HLA^★51 mini-haplotype plays a key role in the immunogenetic molecular mechanisms of Behcet's disease.
Similar studies are under investigation on other inflammatory ocular diseases.
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