| Project/Area Number |
20590800
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Department of Clinical Research, National Hospital Organization Nagasaki Medical Center |
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Principal Investigator |
NAKAMURA Minoru Department of Clinical Research, National Hospital Organization Nagasaki Medical Center, 臨床研究センター, 客員研究員 (40217906)
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| Co-Investigator(Kenkyū-buntansha) |
KOMORI Atumasa 独立行政法人国立病院機構長崎医療センター, 臨床研究センター, 室長 (50234901)
ISHIBASHI Hiromi 独立行政法人国立病院機構長崎医療センター, 臨床研究センター, センター長 (80127969)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 原発性胆汁性肝硬変 / 予後予測 / SNPs / 遺伝子多型 / HLA / 病型分類 / 抗gp210抗体 / 抗セントロメア抗体 / 一塩基多型(SNP) / HLA-DRB1 / 予後 / バイオマーカー / 黄疸型進行 / 非黄疸型進行 / 長期予後診断 |
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| Research Abstract |
In order to establish a clinical classification and a criteria for predicting long-term outcome in primary biliary cirrhosis (PBC), we studied the autoantibodies (anti-gp210, anti-centromere), HLA-DRB1 and SNPs of various molecules concerning immune-regulation and bile acid metabolism. HLA-DRB1*0803 and CTLA4 SNPs confer susceptibility to PBC development. Positive anti-gp210 and anti-centromere antibodies as well as HLA-DRB1*1502 and *0901 are risk factors for the progression to liver cirrhosis or portal hypertension, while positive anti-gp210 antibodies as well as SNPs of MDR3 and integrin ・V are associated with progression to hepatic failure. Since positive anti-gp210 antibodies is a strong risk factor for jaundice-type progression (OR>30), the treatment for PBC became possible with monitoring anti-gp210 antibodies as a serological biomarker. Furthermore, our proposal of PBC progression, anti-gp210 type progression and anti-centromere type progression, was supported by the level of genetic polymorphisms.
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