Studying the association between X gene mutations with hepatocellular carcinoma and liver cirrhosis in HBsAg-positive patients referring to medical centres in Tehran
Abstract number: 1733_983
Hekmat S., Ahmadi Pour M., Amini S., Roohvand F., Alavian S., Joulaie M., Andalibi Mahmoudabadi S.
Objectives: The viral transactivator HBVX (HBx) gene plays a critical role in the molecular pathology of HBV-related HCC. This study investigated the possible HBx mutations in Iranian patients with HCC or liver cirrhosis, especially identification of a point mutation at codon 31 from xORF.
Methods: Sera from 30, 10 and 12 patients with acute hepatitis B, HBV-related HCC and liver cirrhosis, respectively, were analysed by nested-PCR and RFLP methods to detect (HBx-A31) mutation. In addition we also cloned the PCR products from second round of nested PCR in TA cloning vector from 3 HCC, 2 cirrhosis and 2 acute hepatitis subjects followed by sequencing and aligned them with the downloaded sequences from GeneBank. We use neighbour-joining method to make phylogenetic trees.
Results: Two common HBx variants in wild-type HBV, serine-31 (TCG) and praline-31 (CCG), were digested by AvaI in the presence of (T) or (C) at the first nucleotide position of codon 31, the same PCR products were not digested by MwoI in lack of Alanine amino acid (GCG) (a common point mutation at the East Asia). We found two point mutations (nt.1762, nt.1764) and one point mutation into HBV genome from serum of all patients with cirrhosis and HCC. These mutations at both codons 130 (AAG to ATG, lysine to methionine) and 131 (GTC to ATC, valine to isoleucine) were observed in all available HCC cases and located at Basal Core Promoter (BCP) which regulate transcription and production of core and precore RNA. All cases had D genotype and D1 subgenotype (The common genotype in Iran).
Conclusions: Core promoter region have been associated with more-severe liver damage, inflammation and fibrosis. But the implications of these findings in the pathogenesis of HBV are discussed.
|Session name:||European Society of Clinical Microbiology and Infectious Diseases|
|Location:||ICC, Munich, Germany|
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