| Hepatitis B Virus has a strong human pathogenicity in environment. It causes acute and chronic hepatitis, liver cirrhosis, and liver cancer.At the present stage, HBV infection is one of public health problem in China. HBV infection assumes cosmopolitism prevalence. It has distinct geographic distribution. There is highest prevalence of HBsAg (9.09%)in China. Incident rate and fatality of chronic hepatitis B, liver cirrhosis, liver cancer will be increased by it.HBV has mutability and quasispecies characteristics. Now, HBV can be classified into at least eight genotypes (A-H) based on a divergence in the entire nucleotide sequence greater than 8% or S gene nucleotide sequence greater than4%, based on a divergence greater than 4% but less than 8% in the complete nucleotide sequence, HBV genotype has been divided into subgenotypes. HBV genotypes and subgenotypes have a distinct geographical distribution and a close relationship with ethnicity, as well as the relationship with clinical outcomes or responses to antiviral treatment. In China, genotype B and C are the most prevalent HBV strains.HBV showed different geographical distribution in our country, genotype C was predominant in northern China, genotype B was more prevalent in southern provinces. HBV mutation may appear with spontaneous, immunity and drug pressure. According to HBeAg, CHB was divided into HBeAg positive type and HBeAg negative type.PC and BCP mutations lead to HBeAg negative type on clinical manifestations.Long-term nucleoside analogue leads to HBV P genovariation.Recently, HBV genotype has been studied in Xinjiang.There is HBV genotypes, subgenotype distinction between hans and Uygurs. The aim of this article is to study HBV molecular virology and clinical character deeply between hans and uighurs. Object:Xinjiang has its specificity, so it is necessary to study hans and Uygurs HBV molecular virology and clinical character. HBV genotype, subgenotype data will be analysed.PC and BCP regions of HBV genome mutation data and HBV P regions mutation data will be supplied. All of them will help to improve the level of prevention and treatment.Contents:1)To investigate the virological characteristics of these genotype, subgenotypes and their clinical characteristics in Xinjiang hans and Uygurs;2) To investigate the virological features of the precore (PC) and basal core promoter (BCP) regions of the HBV genome and their clinical characteristics in Xinjiang Han and Uygurs;3) To investigate the virological characteristics of P regions mutation of the HBV genome caused by nucleoside analogue antiviral treatment.Method:1) 331 HBV patients collected were from Xinjiang Province.A total of chronic hepatitis B patients with detectable HBV genotypes, subgenotype, PC and BCP regions were detected by PCR-restriction fragment length polymorphism (PCR-RFLP), a part of samples were validated by direct sequencing, nucleotide sequence analysis of the phylogenetic tree, bioinfomatic.2)Randomized 14 samples has been dealed with by whole gene sequencing, 14 samples HBV P regions mutation caused by nucleoside analogue was assayed, 4 samples HBV P regions was assayed, sequence analysis of the phylogenetic tree, bioinfomatic.Results:Collect 331 HBV patients were from Xinjiang Province.A total of chronic hepatitis B patients were detected by PCR-RFLP, a part of samples validate by direct sequencing, nucleotide sequence analysis of the phylogenetic tree, bioinfomatic. 222 hans and 109 Uygurs, mean age±standard deviation, 38.7±12.7 years.1) Amongst 331 HBV patients studied, HBV genotypes showed B genotype 12.7%, C genotype 64%, C/D recombinant 16%, D genotype 7.3%.Compare with Genotype B, Genotype C, recombinant C/ D and Genotype D, they showed the distinctly distribution in Han patients and Uighur patients.Further analysis showed that all genotype B strains belong to Ba subgenotype, Bj subgenotype was not found. Genotype C had two subgenotypes, C1 42.9%, C2 57.1% in Xinjiang. Han HBV genotype showed B 14.9%, C 72.9%, recombinant C/D 9.5%, D 2.7%, Uighur HBV genotype showed B 8.3%, C 45.9%, recombinant C/D 29.4%, D 16.5%. Han HBV subgenotype showed Ba 78.6%, C1 39.5%, C2 60.5% ; Uygurs Ba 21.4%, C1 54%, C2 46%?2) Collect 331 HBV patients were from Xinjiang Province. HBV PC and BCP mutation of total chronic hepatitis B patients were detected by PCR-RFLP, a part of samples were validated by direct sequencing, nucleotide sequence analysis of the phylogenetic tree, bioinfomatic. HBV PC mutation showed PC mutation 30.2%, BCP mutation 34.4%.Further analysis showed C1 was associated with the highest tendency to develop BCP mutation. HBV recombinant C/D was associated with the highest tendency to develop BCP and PC mutation in Uygur.3) 14 samples were defined that the complete HBV genome were sequenced and compared with HBV sequences retrieved from GenBank, representing HBV genotype A-G.. Entire nucleotide sequences revealed that 2 samples were recombinant C/D, 12 samples were genotyped D.Moreover, they had difference sequences. Entire nucleotide sequences of 14 samples were registered.4) HBV P gene of 18 samples was sequenced and compared with HBV sequences retrieved from GenBank, representing HBV genotype A-G..Amongst 14 samples took adefovir, P gene mutation, the esults showed mutation nearby polymerase B(16) and D(6) appeared of 13 samples.Amongst C subgenotype, mutation nearby polymerase B(9) and D(1) with C1 was appeared in 5 samples, mutation nearby polymerase B(3) and D(3) with C2 was appeared in 5 samples, mutation nearby polymerase B(4) and D(8) with Ba was appeared in 6 samples, mutation nearby polymerase B(3) and D(1) with D was appeared in 1 samples, mutation nearby polymerase B(2) with C/D1 was appeared in 1 samples. Genotype B 11.8%, C 64.7%, C/D 20.6%, D 2.9% were showed in 34 YMDD mutation samples.Conclusion:1) Collect 331 HBV patients were from Xinjiang Province.A total of chronic hepatitis B patients were detected by PCR-RFLP, a part of samples validate by direct sequencing, nucleotide sequence analysis of the phylogenetic tree, bioinfomatic. The results showed that the most common HBV genotypes were C and subgenotype C2, while recombinant C/D was also found in Xinjiang. In Uygurs, the most common HBV genotypes were C, C/D and subgenotype C1.Genotype C/D and D have significantly different in Uygurs and Hans. HBV subgenotype C2 was a more important risk factor in hepatocarcinogenesis than other subgenotypes.2) Collect 331 HBV patients were from Xinjiang Province. We studied HBV PC and BCP mutations. The result showed that the PC and BCP mutations have related with subgenotypes. Recombinant C/D has significantly different with Ba in Uygurs.3) 14 samples were defined that the complete HBV genome were sequenced and compared with HBV sequences retrieved from GenBank, representing HBV genotype A-G.. Recombinant C/D was found by above method first time in Xinjiang Han and Uighur. They have been registered in GenBank.4) 18 samples were defined that the HBV P gene was sequenced and compared with HBV sequences retrieved from GenBank, representing HBV genotype A-G..HBV patients with nucleoside analog(ue) has different mutation site in different subgenotype, concentrated nearby polymerase B and D.Uighur HBV patients has particularity in HBV P regions mutations.
|
PDF Full Text Request