B型肝炎病毒Surface基因和重疊Polymerase基因區域之突變頻譜和肝細胞癌危險性：重疊病例對照研究
Mutations in Surface and Overlapping Polymerase Gene Region of Hepatitis B virus and Risk of Hepatocellular Carcinoma: A Nested Case-Control Study
Date Issued
2005
Date
2005
Author(s)
Chang, Li-Ching
DOI
zh-TW
Abstract
Background and Aim: Variations in the viral genome of hepatitis B virus (HBV) has been associated with the clinical outcome of chronic HBV infection, but the significance of these variations in the development of hepatocellular carcinoma (HCC) remains largely unknown. The aim of this study was to longitudinally analyze the nucleotide variations in the PreS/S and overlapping P gene regions of the HBV genome and HCC risk.
Materials and Methods: Direct sequencing of HBV gene was performed on plasma samples from 86 cases and 125 controls nested within a cohort of HBV male carriers recruited between 1988-1992. Controls were matched with cases on the age of entering the study and the time of collection of blood samples at baseline. We also performed sequencing of the HBV gene in plasma samples collected from a total of 17 cases and 27 controls during follow-up. At the second time point, for cases, blood samples collected within two years before the onset of HCC were used. For controls, measuring time was selected according to the nearest blood collecting time of cases.
Results: Compared with adw as the reference sequence, 8 variants were found to have a frequency of ≧ 20% including 2989C, 3050T, 3097A, 3174T in PreS1 region, 35A in PreS2 region, and 285A, 529G, 586C in S region, at baseline samples of controls, the sequence of genotype B was mostly consistent with the adw sequence, except A2989C, C3050T, C3174T and A529G, which occurred at frequency of ≧ 20%. For genotype C, many positions in S region had variant types with prevalence ≧ 20%, especially at nt 85-nt 598 in PreS/S region, the frequency of variant type was ≧ 50%. Difference in nucleotide substitution between case and control groups was everywhere, high variant region was mainly at nt 76-nt 147 in PreS2, which contained 9 variants (including A76C, G85A, G87A, C93T, A96C, A99C, T105C, T109A and G110C) with frequency differences of 15.3%-30.40%. Differences in positions between case and control groups were lower than 6.3% for genotype B. The corresponding figure for genotype C was 37.1%-62.9%. When analysis was limited to these variant positions were still marginally statistically significantly associated with HCC subjects with genotype C. Comparing blood samples at baseline and those at follow-up, higher rate (defined as ≧ 20%) for nucleotide change during follow-up was only observed at three positions nt 2898,nt 3174 and nt 529. Conclusions: Genotype B was mostly consistent with adw sequence, while genotype C had much more variations compared with adw sequence. In most of the PreS/S and overlapping P gene region, nucleotide change was infrequent during long-term follow-up period. Compared with controls, cases had more variant types and high variant region was mainly at nt 76-nt 110 in PreS2 region, where lies within 〝a〞 determinant of HBsAg.
Subjects
B型肝炎病毒
surface基因
polymerase基因
Hepatitis B virus
surface gene
polymerase gene
SDGs
Type
thesis
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