Mutations in the basic core promoter region of hepatitis B virus. Relationship with precore variants and HBV genotypes in a Spanish population of HBV carriers

Jardí, Rosendo; Rodrı́guez, Francisco; Buti, Marı́a; Costa, X.; Valdés, Auristela; Allende, Helena; Schaper, Melanie; Galimany, R.; Esteban, Rafael; Guàrdia, J

doi:10.1016/j.jhep.2003.11.015

Cited by 45 publications

(49 citation statements)

References 40 publications

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“…In contrast to Latvia, the ayw2 subtype was clearly predominant over the ayw3 subtype [47]. Our data also support the postulate, that genotype D is predominant in the Mediterranean region, Southern and Eastern Europe, in such countries as Hungary [48], Italy: 73% of the genotype D, and 26% of the genotype A [49,50], and Spain: 63,2% and 23.1%, respectively [51,52]. In most Western European countries, such as Belgium 54% of genotype A, and 31% of genotype D [53], the Netherlands 64%, and 21% respectively [54] genotype A dominates.…”

Section: Hbv Genotypes In Latvia and Neighboring Countriessupporting

confidence: 88%

Hepatitis B Virus Genotypes in Latvia

Sominskaya¹

2011

TOHEPATJ

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Abstract:The aim of this study was to investigate the properties of HBV genomes isolated from patients with acute and chronic hepatitis, liver cirrhosis, and hepatic coma admitted to the Infectology Center of Latvia. HBV genotypes and HBsAg subtypes were determined by direct S-gene sequencing. Genotypes D (72.17%) and A (27.96%) were predominant. Only one case (0.87%) of HBV genotype E was found. Prevalence of genotype D over genotype A was more strongly pronounced in isolates from patients with acute hepatitis than from patients with chronic hepatitis-74%-24% and 68%-32%, respectively. Number of previously described and some new mutations (Ser21Thr in preC region, Tyr134Lys, Phe134Leu, Ile110Met, Thr118Ile and Ser136Tyr in S-gene) were discovered by direct sequencing of PCR fragments corresponding to preS/S and preC/C regions and to a fragment of the X gene of HBV genome. The most frequently mutations were found in the region of the basal core promoter, preC and major immunodominant region of core protein and domain a of S protein. In general the rate of mutations discovered in chronic patients was just 1,23 times higher then in patients with acute hepatitis, at the same time the ratio for the hot-spot preC 1896 stop mutation was higher and reached 1,81. A possible role of discovered mutations in the HBV pathogenesis is discussed. The findings are relevant to diagnosis and prognosis of HBV-induced liver disease.

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Section: Hbv Genotypes In Latvia and Neighboring Countriessupporting

confidence: 88%

Hepatitis B Virus Genotypes in Latvia

Sominskaya¹

2011

TOHEPATJ

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“…As the assay is able to identify 994 mutations, it was not possible to assemble a panel of samples covering all of them. We established a short list of positions with the highest relevance for HBV biology and disease monitoring (10,23,37). The results obtained at these positions are presented in Table 4 and detailed below.…”

Section: Resultsmentioning

confidence: 99%

“…Mutations in the basal core promoter (BCP) have been associated with fulminant hepatitis and severe disease (10,22,26). In a recent meta-analysis, Liu et al (15) showed that mutations in the pre-S region, as well as in enhancer II of the core (C) gene and BCP, both overlapping with the X gene, are associated with hepatocarcinoma (HCC).…”

mentioning

confidence: 99%

Microarray for Hepatitis B Virus Genotyping and Detection of 994 Mutations along the Genome

et al. 2010

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Genome analysis of hepatitis B virus (HBV) in patient sera is helpful for monitoring treatment. We developed an improved version of a DNA microarray to identify HBV genotypes and to detect mutations of interest in the S, Pol, Core, and X genes. It includes an automated software analysis of fluorescence values for simpler, more robust data interpretation. In this version, probes were added to identify genotype H, to analyze 155 additional positions, and to detect 561 additional polymorphisms. Sequences were added to the alignments to resolve hybridization problems due to natural polymorphisms in the vicinity of important codons. The duplex PCR protocol allowed whole-genome analysis in a single tube. An alternative nested-PCR protocol allowed genotyping and mutations in S and reverse transcriptase (rt) genes in patients with low viral loads, as demonstrated in patients with less than 400 HBV genome copies/ml. Reproducibility was high, with variation coefficients lower than 3%. Only 0.57% of 20,771 codons from 253 samples could not be identified. The concordance with Sanger sequencing for the identification of codons improved from 92.8% to 95.7% with the improved version. Concordance was higher than 91% for codons associated with resistance to lamivudine, emtricitabine, telbivudine, famciclovir, entecavir, and tenofovir with vaccine escape and for pre-Core mutants. Concordance was lower for adefovir resistance mutations (68.6%) and mutations in the basal core promoter (60.3%), probably because hybridization efficiency was affected by the low GC content of the probes. A concordance of 93.7% with sequencing for genotype identification was observed in 190 specimens, lower than that obtained with the first version, possibly due to mixed virus populations.

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“…Precore G1896A mutation was more frequent in patients with fulminant than acute self-limited hepatitis and was independently associated with the fulminant outcome (25). Jardi et al (16) reported that among HBeAg negative CHB, patients with precore G1896A mutation and elevated ALT showed highest HBV DNA, and simultaneous…”

Section: Hepatitis B Virus (Hbv) Infection Is a Global Publicmentioning

confidence: 99%

Prevalence of the precore G1896A mutation in Chinese patients with e antigen negative hepatitis B virus infection and its relationship to pre-S1 antigen

Zhang¹,

Xu²,

Wang³

et al. 2009

Braz. J. Microbiol.

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This study investigated the prevalence of the precore G1896A mutation in Chinese patients with hepatitis B e antigen (HBeAg) negative HBV infection and its relation to serum HBV pre-S1 antigen. The overall prevalence of the precore G1896A mutation was 72.6% in HBeAg-negative Chinese patients with detectable serum HBV DNA. The prevalence of the precore G1896A is significantly higher in Chinese HBeAg-negative patients with chronic hepatitis B than that in inactive HBV carriers with detectable serum HBV DNA. Serum pre-S1 and the precore G1896A mutation were simultaneously detected in most of Chinese HBeAg-negative patients. In most instances, HBeAg-negative chronic hepatitis B is a result of HBV variants in the precore or core promoter region. The HBeAg is encoded by the core gene, which is divided into the precore (PC) region and the core region by two in-frame initiating ATG codons. Transcription of these open reading frames produces the pregenomic RNA that is essential for HBV replication and the PC RNA that translates into HBeAg, which is secreted into the serum (22). Variations

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Mutations in the basic core promoter region of hepatitis B virus. Relationship with precore variants and HBV genotypes in a Spanish population of HBV carriers

Cited by 45 publications

References 40 publications

Hepatitis B Virus Genotypes in Latvia

Hepatitis B Virus Genotypes in Latvia

Microarray for Hepatitis B Virus Genotyping and Detection of 994 Mutations along the Genome

Prevalence of the precore G1896A mutation in Chinese patients with e antigen negative hepatitis B virus infection and its relationship to pre-S1 antigen

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