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Basic Characteristics of Mutations
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Mutation Site
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G1764A |
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Mutation Site Sentence
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The most common mutations in the basal core promoter (BCP) region (A1762T [Thymine], G1764A) can down-regulate, but not abolish, HBeAg production. Contrary to the PC G1896A variant, the BCP variant can be found across all genotypes |
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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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BCP |
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Standardized Encoding Gene
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Genotype/Subtype
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D;A;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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Y |
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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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32860463
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Title
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Precore and Basal Core Promoter Hepatitis B Virus (HBV) Variants Are Present From a Young Age and Differ Across HBV Genotypes
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Author
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Lau DTY,Ganova-Raeva L,Wang J,Mogul D,Chung RT,Lisker-Melman M,Chang KM,Shaikh OS,Janssen HLA,Wahed AS,Lok AS
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Journal
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Hepatology (Baltimore, Md.)
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Journal Info
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2021 May;73(5):1637-1651
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Abstract
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BACKGROUND AND AIMS: Hepatitis B virus (HBV) precore (PC) and dual basal core promoter (BCP) mutations halt and down-regulate hepatitis B e antigen (HBeAg) production respectively. PC mutation is rarely associated with HBV genotype A. We sought to examine the association of these variants with HBV genotypes, age, and HBeAg status in a racially diverse population in North America. Prospective study included 1,036 (808 adults, 228 children) participants in the Hepatitis B Research Network. PC and BCP variants were determined by Sanger sequencing, and dominant HBV species (>50%) were reported. APPROACH AND RESULTS: Median age was 36.3 years (range, 2-80), 44.6% HBeAg(+), 74.2% Asians, 13.3% black, and 9.7% white. The dominant PC variant was present in 29.4% participants, including 20 with subgenotype A1 or A2. Seventeen of 20 participants with genotype A and PC had a compensatory C1858T mutation. In the HBeAg(+) cohort, the prevalence of PC and/or BCP variants increased from 14.4% in the first two decades to 51% after 40 years of age. Among those aged 2-18, 52% and 83% with dominant PC and BCP variants were HBeAg(+) compared to 3.8% and 29% in the >40 years age group. HBeAg clearance rates were significantly higher for those with dominant PC or BCP variants: 24.4 and 15.0 per 100 person-years compared to 6.0 in wild-type HBV (P < 0.0001). CONCLUSIONS: PC variants can be present in HBV genotype A and are usually associated with C1858T, which preserves the pregenome encapsidation sequence. Selection of PC and BCP variants occurred at a young age, with increasing prevalence across age groups. HBeAg(+) participants with dominant PC and BCP variants progressed to the HBeAg(-) phase of chronic HBV infection significantly faster. This finding has potential clinical and therapeutic implications.
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Sequence Data
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-
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