| Project/Area Number |
12670320
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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 |
Hygiene
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| Research Institution | Kobe University |
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Principal Investigator |
KANO Kazutaka (2003) Kobe University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (70111507)
佐藤 茂秋 (2000-2002) 神戸大学, 大学院・医学系研究科, 教授 (00076994)
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| Co-Investigator(Kenkyū-buntansha) |
SAKANE Naoki Kobe University, Graduate School of Medicine, Assistant, 大学院・医学系研究科, 助手 (40335443)
SHIRAKI Takashi Kobe University, Graduate School of Medicine, Assistant, 大学院・医学系研究科, 助手 (10294208)
KAMAE Isao Kobe University, Division of Health Informatics and Science, Professor, 都市安全研究センター, 教授 (70252905)
加納 和孝 神戸大学, 大学院・医学系研究科, 助教授 (70111507)
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| Project Period (FY) |
2000 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | HCV / p53 / hepatocellular carcinoma / somatic mutaions / p53遺伝的多型 / C型肝炎ウイルス / 血小板減少症 / 肝機能検査 / C型肝炎 / 抗体 / RNA / フォローアップ / 血小板 / HCV1b型 / フォーローアップ / 血液検査 / 1b遺伝型 / 感染 / 遺伝的多型 / CCC(Pro) / 肝癌 |
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| Research Abstract |
Hepatitis C virus (HCV) is one of the leading cause of chronic hepatitis, and 20-30% of those infected with HCV develop cirrhosis, a condition preceding hepatocellular carcinoma (HCC). The natural course after HCV infection to the development of HCC is highly variable among individuals.
Existence of somatic mutations of the tumor suppressor gene p53 in HCC has suggested an important role of the p53 on hepatocarcinogenesis. On the other hand, germline variation of p53 at codon 72 has been reported to associate with the susceptibility to various cancers. We previously reported that the p53 proline allele at codon 72 predominates in male subjects infected with HCV genotype 1b compared with non-infected controls. Since several investigations have reported the platelet count as an independent indicator for liver fibrosis and a valuable predictor for a risk of tumorigenesis, we examined the relationship between p53 polymorphism and the progression of thrombopenia by a longitudinal study of the cohort positive for HCV RNA.
To investigate an impact of the tumor suppressor gene p53 polymorphism at codon 72 on the rapid progression of liver injury in chronic hepatitis C virus (HCV) infection, we followed up a cohort positive for HCV RNA between 1997 and 2002. The annual changes of the platelet count, which is a valuable predictor for the hepatic injury in HCV infection, in 54 subjects were compared among the p53 genotypes. The platelet decreased significantly faster in the proline homozygotes compared with the arginine homozygotes (p=0.046). In a multivariate model, the proline homozygous genotype was independently related to the impaired platelet count level (p=0.042 ; odds ratio=6.3). We conclude that the p53 proline homozygosity could be a risk factor for progression of HCV-induced thrombopenia.
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