Genetic Variation in the Core Gene of Hepatitis B Virus and Hepatocellular Carcinoma: A Longitudinal Cohort Study
| Autor: | Feng-Yu Sung, 宋豐伃 |
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| Rok vydání: | 2008 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 96 Background & Aims: HBcAg which is encoded by HBV core gene is immunological target of cytotoxic T cell. Genetic variation in the core gene changes the structure of epitope and escapes immune response. We investigated the association between genetic variation in the HBV core gene and natural history of hepatocellular carcinoma (HCC). Materials & Methods: First, we used sequence data from a nested case-control study to identify genotype-independent single nucleotide polymorphisms (SNPs) associated with HCC. At the second stage, we developed novel TaqMan probes for identification of viral SNPs. Then an investigation was performed with a case-cohort study on the longitudinal stability of SNPs and their effects on the change of viral factors and disease progression over 16 years of follow-up. Results: We found five genotype-independent SNPs inversely associated with the risk of HCC through a scan of the whole core gene region. At baseline, harboring mutants of the above SNPs were associated with a lower plasma HBV DNA levels and HBeAg-positive rate but a higher prevalence of anti-HBe positivity. There was an inverse linear relationship for the accumulation of core gene mutants with HCC risk and HBeAg positivity. During follow-up, mutants exhibited a lower stability than wild type. The emergence of mutants was associated with sustained normalization of ALT and decreased risk of cirrhosis. It was tightly correlated with change in HBV DNA over time. Conclusions: Mutation in the HBV core gene may play some role in the HBeAg seroconversion and HBV replication activity, and thus affect disease progression. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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