Mutations in the S gene and in the overlapping reverse transcriptase region in chronic hepatitis B Chinese patients with coexistence of HBsAg and anti-HBs

Abstract Background The mechanism underlying the coexistence of hepatitis B surface antigen and antibodies to HBsAg in chronic hepatitis B patients remains unknown. Aims This research aimed to determine the clinical and virological features of the rare pattern. Methods A total of 32 chronic hepatitis B patients infected by HBV genotype C were included: 15 carrying both HBsAg and anti-HBs (group I) and 17 solely positive for HBsAg (group II). S gene and reverse transcriptase region sequences were amplified, sequenced and compared with the reference sequences. Results The amino acid variability within major hydrophilic region, especially the “a” determinant region, and within reverse transcriptase for regions overlapping the major hydrophilic region in group I is significantly higher than those in group II. Mutation sI126S/T within the “a” determinant was the most frequent change, and only patients from group I had the sQ129R, sG130N, sF134I, sG145R amino acid changes, which are known to alter immunogenicity. Conclusions In chronic patients, the concurrent HBsAg/anti-HBs serological profile is associated with an increased aa variability in several key areas of HBV genome. Additional research on these genetic mutants are needed to clarify their biological significance for viral persistence.

Mutations in the S gene and in the overlapping reverse transcriptase region in chronic hepatitis B Chinese patients with coexistence of HBsAg and anti-HBs.

BACKGROUND: The mechanism underlying the coexistence of hepatitis B surface antigen and antibodies to HBsAg in chronic hepatitis B patients remains unknown. AIMS: This research aimed to determine the clinical and virological features of the rare pattern. METHODS: A total of 32 chronic hepatitis B patients infected by HBV genotype C were included: 15 carrying both HBsAg and anti-HBs (group I) and 17 solely positive for HBsAg (group II). S gene and reverse transcriptase region sequences were amplified, sequenced and compared with the reference sequences. RESULTS: The amino acid variability within major hydrophilic region, especially the "a" determinant region, and within reverse transcriptase for regions overlapping the major hydrophilic region in group I is significantly higher than those in group II. Mutation sI126S/T within the "a" determinant was the most frequent change, and only patients from group I had the sQ129R, sG130N, sF134I, sG145R amino acid changes, which are known to alter immunogenicity. CONCLUSIONS: In chronic patients, the concurrent HBsAg/anti-HBs serological profile is associated with an increased aa variability in several key areas of HBV genome. Additional research on these genetic mutants are needed to clarify their biological significance for viral persistence.

Association between NCF4 rs4821544T/C polymorphism and inflammatory bowel disease risk in Caucasian: a meta-analysis.

OBJECTIVE: Published studies on the association between NCF4 rs4821544T/C polymorphism and inflammatory bowel disease (IBD) risk in Caucasian have yielded conflicting results. The present study aimed to provide more reliable conclusions by conducting a meta-analysis. METHODS: All eligible studies were extracted from Wiley Online Library, Chinese National Knowledge Infrastructure and PubMed databases. Odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the associations between rs4821544T/C polymorphism and IBD risk in Caucasian. RESULTS: A total of 13 case-control studies comprising 7441 Crohn's disease (CD) patients, 2565 ulcerative colitis (UC) patients and 8315 controls were included in this meta-analysis. Significant associations were found between CD and the rs4821544T/C polymorphism in three genetic models (C vs T: OR = 1.11, 95 % CI: 1.06, 1.16, P = 0.000; CC vs TT: OR = 1.31, 95 % CI: 1.18, 1.45, P = 0.000; CC/TC vs TT: OR = 1.07, 95 % CI: 1.01, 1.13, P = 0.014; CC vs TC/TT: OR = 1.28, 95 % CI: 1.16, 1.42, P = 0.000). However, significant associations were not found in UC under any genetic models (C vs T: OR = 1.04, 95 % CI: 0.97, 1.11, P = 0.264; CC vs TT: OR = 1.10, 95 % CI: 0.93, 1.30, P = 0.284; TC vs TT: OR = 1.04, 95 % CI: 0.95, 1.13, P = 0.429; CC/TC vs TT: OR = 1.04, 95 % CI: 0.95, 1.13, P = 0.390; CC vs TC/TT: OR = 1.07, 95 % CI: 0.91, 1.26, P = 0.409). CONCLUSION: This meta-analysis suggested that the rs4821544T/C polymorphism was associated with CD, but not UC in Caucasian.

Sequence analysis of the HBV S protein in Chinese patients with coexisting HBsAg and anti-HBs antibodies.

The coexistence of hepatitis B surface antigen (HBsAg) and antibodies to HBsAg (anti-HBs) in patients with hepatitis B virus (HBV) infection has been discovered and explained for several decades, but debate still exists. This study was to explore the relationship between this special serological pattern and mutations in S gene region. Fifteen patients with coexisting HBsAg and anti-HBs were selected as the experimental group, and 27 patients with HBsAg positive only were selected as the control group. The S gene region was amplified and sequenced. No significant differences were observed between the two groups with regard to age, gender, alanine aminotransferase level, HBsAg titer, genotype, and HBV DNA level. The patients from the two groups were infected with HBV of the genotype B and C. Compared with the control group, the experimental group showed a higher variability in amino acid within the N-terminal region and the MHR, especially the "a" determinant. The most frequent change in patients from the experimental group was located at positions s126. The coexistence of HBsAg and anti-HBs might be associated with the increased amino acid mutations in the "a" determinant. Further studies should be performed to determine the clinical implication of this serological pattern, including the binding of anti-HBs to HBsAg, escape from immune system, and efficacy of antiviral therapy.

Phosphatase and Tensin Homolog (PTEN) Represses Colon Cancer Progression through Inhibiting Paxillin Transcription via PI3K/AKT/NF-κB Pathway.

The tumor suppressor gene phosphatase and tensin homolog (PTEN) is frequently mutated in colon cancer. However, the potential contribution of loss of PTEN to colon cancer progression remains unclear. In this study, we demonstrated that PTEN overexpression or knockdown in Lovo colon cancer cells decreased or increased paxillin expression, respectively. Moreover, paxillin reversed PTEN-mediated inhibition of Lovo cell invasion and migration. Overexpression of PTEN in an orthotropic colon cancer nude mice model inhibited tumor formation and progression. In addition, PTEN protein level was negatively correlated with that of paxillin in human colon cancer tissues. Mechanistically, we identified three NF-κB binding sites on paxillin promoter and confirmed that paxillin was a direct transcriptional target of NF-κB. Our findings reveal a novel mechanism by which PTEN inhibits the progression of colon cancer by inhibiting paxillin expression downstream of PI3K/AKT/NF-κB pathway. Thereby, PTEN/PI3K/AKT/NF-κB/paxillin signaling cascade is an attractive therapeutic target for colon cancer progression.