Analysis of the core gene of hepatitis B virus in Korean patients

Kim, Hyung Joon; Lee, Dong Hoon; Gwak, Geum‐Youn; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon; Yoo, Byung Chul

doi:10.1111/j.1478-3231.2007.01481.x

Cited by 5 publications

(4 citation statements)

References 24 publications

(26 reference statements)

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“…In addition to the posterior probability value (100), pairwise comparison of the HBV/B genome sequences (Table 3) revealed that the intersubgenotypic divergences of HBV/B9 against B1, B6, B2 and B4 were significantly higher than the suggested 4% as the distinguishing divergence for subgenotypes [20] (6.07 ± 0.49, 5.87 ± 0.29, 4.86 ± 0.37, and 4.82 ± 0.45, respectively). Although the divergences were less against B5, B8, B7 and B3 (3.43 ± 0.25, 3.22 ± 0.24, 3.21 ± 0.31, and 3.07 ± 0.24, respectively), we argue that consideration of the distinct geographical and host ethnicity association [21], in addition to the phylogenetic and genetic distance data, define the unidentified cluster as a distinct subgenotype.…”

Section: Discussionmentioning

confidence: 99%

Ethnogeographical structure of hepatitis B virus genotype distribution in Indonesia and discovery of a new subgenotype, B9

et al. 2011

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The distribution of hepatitis B virus (HBV) in the populations of island Southeast Asia is of medical and anthropological interest and is associated with an unusually high genetic diversity. This study examined the association of this HBV genetic diversity with the ethnogeography of the populations of the Indonesian archipelago. Whole genome analysis of 21 HBV isolates from East Nusa Tenggara and Papua revealed two recently reported HBV/B subgenotypes unique to the former, B7 (7 isolates) and B8 (5 isolates), and uncovered a further novel subgenotype designated B9 (4 isolates). Further isolates were collected from 419 individuals with defined ethnic backgrounds representing 40 populations. HBV/B was predominant in Austronesian-language-speaking populations, whereas HBV/C was the major genotype in Papua and Papua-influenced populations of Moluccas; HBV/B3 was the predominant subgenotype in the western half of the archipelago (speakers of the Western Malayo-Polynesian [WMP] branch of Austronesian languages), whereas B7, B8 and B9 were specific to Nusa Tenggara (Central Malayo-Polynesian (CMP)). The result provides the first direct evidence that the distribution of HBV genotypes/subgenotypes in the Indonesian archipelago is related to the ethnic origin of its populations and suggests that the HBV distribution is associated with the ancient migratory events in the peopling of the archipelago.Electronic supplementary materialThe online version of this article (doi:10.1007/s00705-011-0926-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Ethnogeographical structure of hepatitis B virus genotype distribution in Indonesia and discovery of a new subgenotype, B9

et al. 2011

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“…It contains CTL epitopes, T-helper cell epitopes, and B-cell recognition sites (21)(22)(23). Although a variety of mutations may emerge in C genes during the immune clearance phase, only a few mutations within or flanking the HBcAg epitopes have been reported to be of clinical relevance (24)(25)(26). About the association of the C gene mutations and HCC, Sung et al (25) reported that mutations at nts 1961, 1938, 2045, 2136, 2239, and 2441 were associated with decreased risk for HCC, whereas no mutation in the C gene was found to be related to an increased risk for HCC in Taiwan.…”

Section: Discussionmentioning

confidence: 99%

Comparison Study on the Complete Sequence of Hepatitis B Virus Identifies New Mutations in Core Gene Associated with Hepatocellular Carcinoma

Zhu

Yan

Guo

et al. 2010

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Mutations in the hepatitis B virus (HBV) genome may influence the activity of liver disease. The aim of this study was to identify new viral variations associated with hepatocellular carcinoma (HCC).Methods: We carried out a comparison study on the complete sequence of HBV isolated from 20 HCC and 35 non-HCC patients in Qidong, China, an area with a high incidence of HCC. We compared the HBV sequences in a consecutive series of plasma samples from four HCC cases before and after the occurrence of HCC. In addition, we selected four mutations in the HBV core (C) gene to verify their relationships to HCC in an independent set of 103 HCC cases and 103 sex-and age-matched non-HCC controls.Results: The pre-S deletion and 12 point mutations, namely, the pre-S2 start codon mutation, T53C in the pre-S2 gene, T766A in the S gene, G1613A, C1653T, A1762T, G1764A in the X gene, and G1899A, C2002T, A2159G, A2189C, and G2203W (A or T) in the pre-C/C gene, showed close associations with HCC. In the validation study, A2159G, A2189C, and G2203W showed consistent associations with HCC by univariate analysis. Multivariate analysis showed that A2189C and G2203W were independent risk factors for HCC. The odds ratios (95% confidence interval) were 3.99 (1.61-9.92) and 9.70 (1.17-80.58), respectively, for A2189C and G2203W.Conclusions: These results implicate A2189C and G2203W as new predictive markers for HCC. Impact: The complete genome analysis of HBV provided pilot data for the identification of novel mutations that could serve as markers for HCC. Cancer Epidemiol Biomarkers Prev; 19(10); 2623-30. ©2010 AACR.

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“…Significantly, we discovered a critical polymorphism c59I/V within the 183 amino acids of HBcAg distinguishing HBV/C into the Asian and Papua-Pacific types, with the exception of C14 that has Papua-Pacific c59V characteristics ( Fig 3 ). This c59I/V polymorphism warrants further study since it is located in the highly immunogenic T helper epitopes [ 33 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…HBV genetic diversity has been suggested to be associated with natural selection influenced by host ethnic-related genetic background [ 30 ], reflected by divergence of amino acid substitutions within certain regions of HBV structural proteins, particularly HBsAg and the core (HBcAg) antigens [ 31 ]. These two proteins are important because HBsAg contains T cell and B cell epitopes that define HBV variants [ 32 – 34 ], while HBcAg possesses immunologic targets of host immune response that determine the course of HBV infection [ 31 , 35 ]. Several Human Leukocyte Antigen (HLA)-restricted T cell epitopes within HBsAg and HBcAg have been proposed and different epitopes may present in consequence of the diverse distribution of HLA in populations in distinct geographical regions [ 36 ].…”

Section: Introductionmentioning

confidence: 99%

Genogeography and Immune Epitope Characteristics of Hepatitis B Virus Genotype C Reveals Two Distinct Types: Asian and Papua-Pacific

Thedja

Muljono

et al. 2015

PLoS ONE

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Distribution of hepatitis B virus (HBV) genotypes/subgenotypes is geographically and ethnologically specific. In the Indonesian archipelago, HBV genotype C (HBV/C) is prevalent with high genome variability, reflected by the presence of 13 of currently existing 16 subgenotypes. We investigated the association between HBV/C molecular characteristics with host ethnicity and geographical distribution by examining various subgenotypes of HBV/C isolates from the Asia and Pacific region, with further analysis on the immune epitope characteristics of the core and surface proteins. Phylogenetic tree was constructed based on complete HBV/C genome sequences from Asia and Pacific region, and genetic distance between isolates was also examined. HBV/C surface and core immune epitopes were analyzed and grouped by comparing the amino acid residue characteristics and geographical origins. Based on phylogenetic tree and geographical origins of isolates, two major groups of HBV/C isolates—East-Southeast Asia and Papua-Pacific—were identified. Analysis of core and surface immune epitopes supported these findings with several amino acid substitutions distinguishing the East-Southeast Asia isolates from the Papua-Pacific isolates. A west-to-east gradient of HBsAg subtype distribution was observed with adrq+ prominent in the East and Southeast Asia and adrq- in the Pacific, with several adrq-indeterminate subtypes observed in Papua and Papua New Guinea (PNG). This study indicates that HBV/C isolates can be classified into two types, the Asian and the Papua-Pacific, based on the virus genome diversity, immune epitope characteristics, and geographical distribution, with Papua and PNG as the molecular evolutionary admixture region in the switching from adrq+ to adrq-.

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Analysis of the core gene of hepatitis B virus in Korean patients

Abstract: Core gene substitutions were more frequently detected in HBeAg-negative and/or HBV DNA-negative patients. The substitutional hot spots were codons 87, 97, 112 and 130; substitutions at these codons might play a role in immune-modulation during the course of chronic HBV infection.

Cited by 5 publications

References 24 publications

Ethnogeographical structure of hepatitis B virus genotype distribution in Indonesia and discovery of a new subgenotype, B9

Ethnogeographical structure of hepatitis B virus genotype distribution in Indonesia and discovery of a new subgenotype, B9

Comparison Study on the Complete Sequence of Hepatitis B Virus Identifies New Mutations in Core Gene Associated with Hepatocellular Carcinoma

Genogeography and Immune Epitope Characteristics of Hepatitis B Virus Genotype C Reveals Two Distinct Types: Asian and Papua-Pacific

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