Sequential accumulation of the mutations in core promoter of hepatitis B virus is associated with the development of hepatocellular carcinoma in Qidong, China

Guo, Xiaokui; Yan, Jing; Gao, Qian; Tu, Hong

doi:10.1016/j.jhep.2008.06.026

Cited by 74 publications

(79 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The cycling parameters were the same as that for S gene amplification, except with an elongation time of 1 min. A nested PCR was performed for PCR negative samples using primers HB1 and HB3 for the first round PCR [35 cycles: denaturation at 95℃ (1 min), annealing at 48℃ (30 s) and elongation at 72℃ (1 min)] and using primers HB2 and HB3 for the second round PCR with the same parameters as the first-round PCR, but the annealing temperature was 46℃, as described previously [37] . Both sets of primers could amplify the full HBx gene.…”

Section: Samplesmentioning

confidence: 99%

Hepatitis B virus subgenotypes and basal core promoter mutations in Indonesia

Utama¹,

Purwantomo

Siburian

et al. 2009

WJG

View full text Add to dashboard Cite

AIM:To identify the distribution of hepatitis B virus (HBV) subgenotype and basal core promoter (BCP) mutations among patients with HBV-associated liver disease in Indonesia. METHODS:Patients with chronic hepatitis (CH, n = 61), liver cirrhosis (LC, n = 62), and hepatocellular carcinoma (HCC, n = 48) were included in this study.HBV subgenotype was identified based on S or preS gene sequence, and mutations in the HBx gene including the overlapping BCP region were examined by direct sequencing. RESULTS:HBV genotype B (subgenotypes B2, B3, B4, B5 and B7) the major genotype in the samples, accounted for 75.4%, 71.0% and 75.0% of CH, LC and HCC patients, respectively, while the genotype C (subgenotypes C1, C2 and C3) was detected in 24.6%, 29.0%, and 25.0% of CH, LC, and HCC patients, respectively. Subgenotypes B3 (84.9%) and C1 (82.2%) were the main subgenotype in HBV genotype B and C, respectively. Serotype adw2 (84.9%) and adrq+ (89.4%) were the most prevalent in HBV genotype B and C, respectively. Double mutation (A1762T/G1764A) in the BCP was significantly higher in LC (59.7%) and HCC (54.2%) than in CH (19.7%), suggesting that this mutation was associated with severity of liver disease. The T1753V was also higher in LC (46.8%), but lower in HCC (22.9%) and CH (18.0%), suggesting that this mutation may be an indicator of cirrhosis. CONCLUSION:HBV genotype B/B3 and C/C1 are the major genotypes in Indonesia. Mutations in BCP, such as A1762T/G1764A and T1753V, might have an association with manifestations of liver disease.

show abstract

Section: Samplesmentioning

confidence: 99%

Hepatitis B virus subgenotypes and basal core promoter mutations in Indonesia

Utama¹,

Purwantomo

Siburian

et al. 2009

WJG

View full text Add to dashboard Cite

show abstract

“…In contrast, the adjacent V1753 or A1768 mutation significantly increased the risk of HCC. Recently, a longitudinal study demonstrated that T1762/A1764 mutation could be detected 4-7 years prior to HCC in most cases, while T1766/A1768 mutation occurred only at or near the stage of HCC, suggesting T1766/ A1768 may be a more valuable predictive marker for HCC [31]. Because several reports demonstrated that T1766/A1768 mutation enhanced viral replication [29,32], high viral load caused by this mutation might contribute to hepatocarcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Accumulation of the Mutations in Basal Core Promoter of Hepatitis B Virus Subgenotype C1 Increase the Risk of Hepatocellular Carcinoma in Southern China

Chen

et al. 2013

J Clin Exp Pathol

View full text Add to dashboard Cite

Hepatitis B virus (HBV) genotype C is associated with the development of hepatocellular carcinoma (HCC). In addition, HBV subgenotype C1 is the major subgenotype in Southern China. The aim of this study was to investigate whether there was the specific mutation patterns in HBV/C1 associated with Southern Chinese patients with HCC. Methods: Mutations in HBV basal core promoter (BCP) and their association with HCC were assessed in a matched cross-sectional control study of 102 HCC and 105 chronic hepatitis (CH) patients (from Guangdong, China) infected with HBV/C1. Functional analysis of HBx mutants was performed by the colony formation assay and the luciferase assays. Results: T1762/A1764 double mutations was frequently found in patients infected with HBV/C1, regardless of clinical status (64.7% in HCC and 51.4% in CH, P>0.05). Unexpectedly, the adjacent V1753 or A1768 mutation significantly increased the risk of HCC (P<0.05). Moreover, the prevalence of triple or quadruple mutations in BCP was significantly higher in patients with HCC than those with CH, particularly for HBeAg-positive-carriers (P<0.05). Functional analysis revealed that T1762/A1764 mutation alone did not alter the transcriptional activity and the inhibitory effects on cell proliferation of HBx, but triple or quadruple mutations largely abrogated this effect. Conclusions: Accumulation of mutations involving V1753 or/and A1768 in addition to T1762/A1764 in BCP region were closely related to HCC among the patients infected with HBV/C1, particularly for HBeAg-positive-carriers. The increased risk of HCC caused by BCP variants may be attributable partially to modifying the biological functions of HBx.

show abstract

“…For instance, the T-cell response to HBx-derived epitopes, including K130 and V131, could play a role in the selection of the double mutants (Malmassari et al, 2007). Secondly, it is possible that the BCP mutations in the X gene might contribute to the progression of liver diseases, as both BCP mutations were found to be strongly associated with severe liver diseases, in particular, HCC (Baptista et al, 1999;Baumert et al, 1996;Guo et al, 2008;Kao et al, 2003). Importantly, recent retrospective analysis of patients with chronic HBV infection has indicated that the BCP1 mutation is strongly associated with HCC with an odds ratio of 30 (Liu et al, 2006).…”

Section: Discussionmentioning

confidence: 99%