Influence of hepatitis B virus core promoter mutations on hepatocellular carcinoma among Japanese patients
| Project/Area Number |
18590741
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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 | Nagoya City University |
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Principal Investigator |
TANAKA Yasuhito Nagoya City University, Graduate School of Medical Sciences, Associate Professor (90336694)
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| Co-Investigator(Kenkyū-buntansha) |
KONDA Yutaka Aichi Cancer Center, Division of Molecular Oncology, Chief (00419897)
YOSHIZAWA Hiroshi Hiroshima University, Graduate School of Biomedical Sciences, Professor (30109954)
MIZOKAMI Masashi Nagoya City University, Graduate School of Medical Sciences, Professor (40166038)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2006: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | Hepatitis B virus (HBV) / HBV genotype / core promoter Mutation / Hepatocellular carcinoma / Hepatitis B Viral replication / Chimeric mice / HBV genotype / ウイルス複製 |
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| Research Abstract |
Viral differences in enhancer II/core promoter and precore regions between the subgenotypes and their association with hepatocellular carcinoma (HCC) were assessed in 3 independent studies; 1)a matched cross-sectional control study of 118 carriers with HBV/C1/Cs and 210 HBV/C2/Ce; 2) a control study among 8 IC and 8 HCC patients infected with HBV genotype C before and after seroconversion; 3)an age, sex, and HBeAg status matched cross-sectional control study between 80 Japanese patients infected with HBV/C2 with HCC and 80 without HCC. Our data indicate that T1653 and/or V1753 mutations in addition to T1762/A1764 are strongly associated with HCC in context of HBeAg status among HBV/C-carriers. HBV/C subgenotypes have specific mutation patterns, which is probably responsible for increased carcinogenesis of HBV/C2/Ce.
HBV of various genotypes may induce liver disease of distinct severity, but the underlying virological differences are not well defined. Huh7 cells were transfected with plasmids carrying 1.24-fold the HBV genome of different genotypes/subgenotypes (2 strains each for Aa/A1, Ae/A2, Ba/B2 and D; 3 each for Bj/B1 and C). uPA/SCID mice with human hepatocytes were inoculated with mouse passages of virions recovered from culture supernatants. Serum levels of HBV DNA in these mice were higher for C than Ae by 2 logs during 4-7 weeks post-inoculation. In conclusion, virological differences among HBV genotypes were demonstrated both in tissue culture and chimeric mice. These differences may influence HBV infections with distinct genotypes in clinical and epidemiological settings.
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Report
(3 results)
Research Products
(52 results)
