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Basic Characteristics of Mutations
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Mutation Site
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T184S |
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Mutation Site Sentence
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RtM204V clusters with mutations localized in the RT-B domain (rtV173L, rtL180M, and rtT184A/S) (bootstrap=0.94), while rtM204I clusters with mutations localized in the RT-A domain (rtS53N, rtT54Y, and rtL80I/V) (bootstrap=0.96) (without associations with HBsAg specific mutations). |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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RT |
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Standardized Encoding Gene
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P
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Genotype/Subtype
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D |
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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 Virus Infection
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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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- |
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Treatment
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Lamivudine(LAM) |
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Location
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Italy |
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Literature Information
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PMID
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19041149
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Title
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The profile of mutational clusters associated with lamivudine resistance can be constrained by HBV genotypes
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Author
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Svicher V,Gori C,Trignetti M,Visca M,Micheli V,Bernassola M,Salpini R,Gubertini G,Longo R,Niero F,Ceccherini-Silberstein F,De Sanctis GM,Spano A,Cappiello G,Perno CF
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Journal
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Journal of hepatology
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Journal Info
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2009 Mar;50(3):461-70
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Abstract
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BACKGROUND/AIMS: To investigate the different clusters of mutations associated with lamivudine resistance in HBV genotypes D and A. METHODS: HBV reverse transcriptase sequences of 89 HBV-infected patients failing lamivudine treatment were analyzed. The association of mutations with HBV genotypes was assessed by Chi-Squared test and multivariate logistic regression analysis. Covariate analysis was based on hierarchical clustering. RESULTS: In genotype A, the rtM204V (prevalence: 68.2%) was the main sign of lamivudine failure. Multivariate analysis confirmed that genotype A is the only predictor for rtM204V emergence (OR: 14.5 [95% CI: 1.3-158], P=0.02). Covariate analysis showed that rtM204V clusters with rtL180M, rtL229V (corresponding to sF220L in the HBsAg), and, interestingly, with HBsAg mutation sS207N (bootstrap=0.95). Both sF220L and sS207N co-localized in the fourth transmembrane HBsAg domain. In contrast, in genotype D the primary mutations rtM204V and rtM204I occurred with similar prevalence (39.1% versus 45.3%, P=0.47), and showed a distinct pattern of compensatory mutations. rtM204V clusters with mutations localized in the RT-B domain (rtV173L, rtL180M, and rtT184A/S) (bootstrap=0.94), while rtM204I clusters with mutations localized in the RT-A domain (rtS53N, rtT54Y, and rtL80I/V) (bootstrap=0.96) (without associations with HBsAg specific mutations). CONCLUSIONS: HBV genotype plays an important role in driving RT evolution under lamivudine treatment, and thus can be relevant for therapeutic sequencing, immunological response and disease progression.
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Sequence Data
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-
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