| Hepatitis B virus (HBV) genome contains four open reading frames (ORF), including S-ORF, C-ORF, P-ORF and X-ORF. C-ORF encode FffieAg and HBcAg. The regulatory sequences of C-ORF are located in HBV precore and core promoter region. In this region, the well-defined mutations including precore mutation at A1896 (ntl896G-*A) and core promoter double mutations at T1762 (nt!762A^T) and A1764 (nt!764G^ A) are associated with the FffieAg-negative HBV infection. However, it is not certain whether these mutations are interrelated with clinical courses. The other 2 mutations in core promoter at T 1653 (ntl653C-*T) and C1753 (ntl753Tæ¡Ÿ) had been found in patients with hepatic failure. But the develop pattern of these mutations is unclear. The clinical meaning of above-mentioned HBV mutations needs more research data to illustrate, including contrast of different areas and different groups. In addition, it is necessary to study the exist pattern and relations with every mutations in precore and core promoter regions deeply because there are many regulatory sequences among these regions.In this study serum HBV samples were obtained from 20 patients with chronic hepatitis and 25 patients with chronic hepatic failure in Zhejiangprovince. The entire nucleotide sequence of precore and core promoter regions (ntl 606-2016) were determined in all 45 cases by polymerase chain reaction (PCR) and direct sequencing method. The "hot spot" mutations would be affirmed and new mutation spots might be found besides "hot spot" mutations. Moreover, the association among mutations was studied to explore the clinicl significance of mutations in precore and core promoter regions.The main HBV mutation spots in precore and core promoter regionsPrecore A1896 mutants were identified in 24 (53.3%) of 45 isolates, and displayed a T1858 exclusively which accounts for the high prevalence of A1896 among the isolates in Zhejiang province: A1896 pairing with T1858 ensure a stable e stem-loop region of the encapsidation signal in the course of HBV replication.The most common core promoter mutations involve T1762 and A1764, which present together in 27 (60%) of 45 isolates, while the other two mutations at T1653 and C1753 existed in a mutually exclusive manner. The tendency above was inferred to be related to X gene overlapping core promoter region. It requires further study whether these mutations were selected by transactivating activity of X gene or by immune escape of HBV under host immune pressure.The comparison of main HBV mutations in precore and core promoter regions between patients with chronic hepatitis and hepatic failure.The development of A1896 mutation in precore region was found to have no significant difference between chronic hepatitis patients and hepatic failure patients (40% vs. 64%, P>0.05). So it may exhibit no associationwith disease activity, and be not the charactistic mutation in patients with hepatic failure.T1762-A1764 double mutations in core promoter region accompanied by precore 1896A mutation were found exclusively in patients with hepatic failure (44%). T1653/C1753 single mutation was also found in patients with hepatic failure (72%), and accompanied by T1762-A1764 double mutations. It probably suggested that mutations in core promoter were to be relevant to disease activity. Whether the T1762-A1764 mutants being followed by A1896 or T1653/C1753 single mutation would influence host immune response and result in hepatic failure remains to be studied deeply.Conclusion1. The main mutation in precore region of HBV isolated from patients in Zhejiang province was A1896. The main mutations in core promoter include T1653, C1753, T1762 and A1764.2. The development of A1896 mutation in precore region depends on the distribution of HBV genotype with T1858 pattern among different epidemic areas, and is irrelevant directly to clinical course.3. There are multiple-spot mutations in HBV core promoter. T1762 and A1764 present together, while T1653 and C1753 exist in a mut...
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