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Mutations in pre-core and basal-core promoter regions of hepatitis B virus in chronic HBV patients from Golestan, Iran.

ABSTRACT: OBJECTIVES:It has been reported that the mutation of the pre-core (PC) and basal-core promoter (BCP) may play an important role in the development of HBV-related hepatocellular carcinoma (HCC). In this study the PC and BCP mutations were investigated in chronic HBV patients. MATERIALS AND METHODS:In this study, 120 chronic HBV patients from Golestan, Northeast of Iran who were not vaccinated against HBV, were recruited from the year 2008 to 2012. HBV-DNA extraction from plasma and PCR were performed and positive PCR products were subjected to automated sequencing. RESULTS:One hundred out of 120 (83.3%) patients were HBeAg negative. Comparison of our nucleotide sequences with reference sequence showed high rate mutation in BCP and PC region (96.66%). Frame shift mutation was found in 78 (65%) of patients in BCP region, among them 8 (6.6%) patients showed mutation in PC region. CONCLUSION:Our results demonstrated high rate of mutations in BCP and PC regions among HBV chronic patients in Northeast of Iran.

SUBMITTER: Moradi A

PROVIDER: S-EPMC4069846 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Mutations in pre-core and basal-core promoter regions of hepatitis B virus in chronic HBV patients from Golestan, Iran.

Moradi Abdolvahab A Zhand Sareh S Ghaemi Amir A Javid Naeme N Bazouri Masoud M Tabarraei Alijan A

Iranian journal of basic medical sciences 20140501 5

<h4>Objectives</h4>It has been reported that the mutation of the pre-core (PC) and basal-core promoter (BCP) may play an important role in the development of HBV-related hepatocellular carcinoma (HCC). In this study the PC and BCP mutations were investigated in chronic HBV patients.<h4>Materials and methods</h4>In this study, 120 chronic HBV patients from Golestan, Northeast of Iran who were not vaccinated against HBV, were recruited from the year 2008 to 2012. HBV-DNA extraction from plasma and ...[more]

PMID: 24967066

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Project description:BackgroundWe recently reported complex hepatitis B virus (HBV) drug resistant and concomitant vaccine escape hepatitis B surface antigen (HBsAg) variants during human immunodeficiency virus (HIV) co-infection and antiretroviral therapy (ART) exposure in Ethiopia. As a continuation of this report using the HBV positive sera from the same study participants, the current study further analyzed the HBV basal core promoter (BCP)/precore (PC) genes variability in patients with HBV drug resistance (at tyrosine-methionine-aspartate-aspartate (YMDD) reverse transcriptase (RT) motifs) and HIV co-infection in comparison with HBV mono-infected counterparts with no HBV drug resistant gene variants.Materials and methodsA total of 143 participants of HBV-HIV co-infected (n = 48), HBV mono-infected blood donors (n = 43) and chronic liver disease (CLD) patients (n = 52) were included in the study. The BCP/PC genome regions responsible for HBeAg expression from the EcoRI site (nucleotides 1653-1959) were sequenced and analyzed for the BCP/PC mutant variants.ResultsAmong the major mutant variants detected, double BCP mutations (A1762T/G1764A) (25.9%), Kozak sequences mutations (nt1809-1812) (51.7%) and the classical PC mutations such as A1814C/C1816T (15.4%), G1896A (25.2%) and G1862T (44.8%) were predominant mutant variants. The prevalence of the double BCP mutations was significantly lower in HIV co-infected patients (8.3%) compared with HBV mono-infected blood donors (32.6%) and CLD patients (36.5%). However, the Kozak sequences BCP mutations and the majority of PC mutations showed no significant differences among the study groups. Moreover, except for the overall BCP/PC mutant variants, co-prevalence rates of each major BCP/PC mutations and YMDDRT motif associated lamivudine (3TC)/entecavir (ETV) resistance mutations showed no significant differences when compared with the rates of BCP/PC mutations without YMDD RT motif drug resistance gene mutations. Unlike HIV co-infected group, no similar comparison made among HBV mono-infected blood donors and CLD patients since none of them developed the YMDD RT motif associated 3TC/ETV resistance mutations. However, HBV mono-infected blood donors and CLD patients who had no any drug resistance gene variants developed comparable G1862T (60.6% vs. 65.1%) and G1896A (24.2% vs. 11.6%) PC gene mutations.ConclusionNo correlation observed between the BCP/PC genome variability and the YMDD RT motif associated HBV drug resistance gene variants during HIV co-infection. Nevertheless, irrespective of HIV co-infection status, the higher records of the BCP/PC gene variability in this study setting indicate a high risk of potential HBeAg negative chronic HBV infection in Northwest Ethiopia.

Dataset Information

Mutations in pre-core and basal-core promoter regions of hepatitis B virus in chronic HBV patients from Golestan, Iran.

Publications

Mutations in pre-core and basal-core promoter regions of hepatitis B virus in chronic HBV patients from Golestan, Iran.

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