Plenary Submissions| Volume 3, ISSUE 1, SUPPLEMENT , S1, March 2013

Downregulation of HMGB1 and PARP1 Genes in Inactive Carriers of Hepatitis B Virus Infection: Suggesting Enhanced Viral Integration

      Plenary session

      Background: Inactive carriers of Chronic HBV infection are at a risk of developing hepatocellular carcinoma (HCC). High mobility group box 1(HMGB1) and Poly (ADP-ribose) polymerase-1(PARP-1) proteins repair cellular DNA damage and maintain genomic integrity. One of the factors favoring integration of Hepatitis B virus (HBV) DNA into host genome is increased frequency of cellular DNA damage resulting in the development of HCC.
      Aims: This study was performed to assess the expression of HMGB1 and PARP1mRNAs along with the estimation of HBV pre genomic RNA (Pg RNA) as replication intermediate in different phases of HBV infection namely to acute (AHB), inactive carriers (IC), cirrhosis (cirr) and HCC.
      Methods: Eighty-eight patients and 26 voluntary blood donors as controls were included in the study. Patients were grouped in to acute (AHB; n=15), inactive carriers (IC; n=36), cirrhosis (Cirr; n=25) and hepatocellular carcinoma (HCC; n=12) respectively. Quantification of serum HBV DNA was done by real time polymerase chain reaction (PCR) assay. Expression of HMGB1, PARP1 and Pg RNA was evaluated in peripheral blood mononuclear cells (PBMCs) derived RNA by reverse transcription PCR (RT-PCR) assay.
      Results: Expression of both HMGB1 and PARP1 genes were significantly reduced in patients than in controls (P<0.05) with reduction of PARP1 being more pronounced in patients (P=0.0002). While the level of Pg RNA a replication intermediate showed significant downregulation (P<0.001) in IC group as compared to acute (AHB), cirrhosis (cirr) and HCC.
      Conclusion: Our findings indicate that ICs having impaired DNA damage repair mechanism are more susceptible to cellular DNA damage. This facilitates enhanced integration of HBV DNA in to host genome, a prerequisite for HCC development.