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Basic Characteristics of Mutations
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Mutation Site
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A135C |
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Mutation Site Sentence
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Importantly, the frequencies of significant HBV mutations (A1C, A31T, T49A, A52C, G105C, C109A, A135C, and G147C in genotype B and A1C, C7A, C10A, A31T, T49A, A52C, G105C, C109A, A135C, and G147C in genotype C) in the pre-S2 region were extremely low (0.0% in genotype B and 0.0% to 4.2% in genotype C) in ASCs but equally high in the CHB patients, HC patients, and HCC patients (92.3% to 100.0% in genotype B and 89.7% to 100.0% in genotype C). |
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Mutation Level
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Nucleotide level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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PreS2 |
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Standardized Encoding Gene
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S
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Genotype/Subtype
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B;C |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Hepatitis B, Chronic
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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Y |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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24006435
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Title
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HLA-DP polymorphisms affect the outcomes of chronic hepatitis B virus infections, possibly through interacting with viral mutations
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Author
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Zhang Q,Yin J,Zhang Y,Deng Y,Ji X,Du Y,Pu R,Han Y,Zhao J,Han X,Zhang H,Cao G
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Journal
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Journal of virology
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Journal Info
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2013 Nov;87(22):12176-86
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Abstract
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Genetic polymorphisms of HLA-DP have been associated with hepatitis B virus (HBV) persistence. We aimed to determine the effect of HLA-DP polymorphisms on the generation of HBV mutations and their interactions on the outcomes of HBV infection. rs3077, rs3135021, rs9277535, and rs2281388 were genotyped in 1,342 healthy controls, 327 HBV clearance subjects, and 2,736 HBV-positive subjects, including 1,108 hepatocellular carcinoma (HCC) patients, using quantitative PCR. HBV mutations were determined by sequencing. Multiplicative interactions of HLA-DP polymorphisms and viral mutations were assessed by multivariate logistic regression. rs3077 (from subjects with genotype CT combined with those from subjects with genotype TT [CT+TT] versus CC), rs3135021 (GA+AA versus GG), rs9277535 (GA+AA versus GG), and rs2281388 (CC versus CT+TT) significantly decreased HBV persistence. This effect was found only in genotype B HBV-infected subjects compared to HBV clearance subjects. HLA-DP polymorphisms promoting HBV clearance were associated with a lower prevalence of mutations increasing HCC risk (C1653T, T1674C/G, A1846T, G1896A and pre-S2 mutations and pre-S deletion in genotype C) and a higher prevalence of mutations decreasing HCC risk (G1652A, T1673C, T1674C, G1719T, G1730C, and G1799C in genotype B and A1727T in genotype C). Significant effects of viral mutations on cirrhosis and HCC were selectively evident in those with HLA-DP polymorphisms promoting HBV persistence. The interactions of C1653T, T1674C/G, and G1896A mutations with HLA-DP polymorphisms promoting HBV clearance significantly decreased cirrhosis risk. The interaction of rs9277535 AA with the T1674C/G or G1719T mutation in genotype C significantly decreased HCC risk. In conclusion, HLA-DP polymorphisms affect genotype B HBV clearance, regulate immune selection of viral mutations, and influence cirrhosis and HCC risks contributed by HBV mutations.
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Sequence Data
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KC934199-KC934467;KC934468-KC934744
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