The association of Manganese superoxide dismutase gene polymor-phism with the prognosis of Hepatitis C Virus related hepatocellular carcinoma patients
The association of Manganese superoxide dismutase gene polymor-phism with the prognosis of Hepatitis C Virus related hepatocellular carcinoma patients
Mai A. Kilany1; Hanaa H.A. Gomaa1; Yousry E. Abo El-magd2 and Nermin Raafat2.
ABSTRACT
Hepatitis C virus (HCV) is a hepatotropic RNA virus that causes acute and chronic hepatitis in humans with a high propensity for chronicity. If untreated, chronic hepatitis C can progress to cirrhosis and hepatocellular carcinoma (HCC) in a subset of patients. HCC is a prevalent disease in many populations worldwide. It causes many financial problems in treatment modalities with high mortality rates. In develop-ing countries, the major concern in HCC frequently belongs to HCV long lasting in-fection. Chronic HCV infection mostly leads to hepatic cirrhosis before developing HCC. HCV infection induces overproduction of reactive oxygen species (ROS) in hepatocytes leading to their proliferation and triggers HCC. Manganese superoxide dismutase (MnSOD) is a nuclear-encoded antioxidant enzyme that neutralizes free radicals. Val16Ala single nucleotide polymorphism (SNP) is one of the most widely investigated SNPs in the MnSOD gene, where C to T transition resulting in the con-version of valine to alanine at amino acid 16 within the mitochondrial signaling se-quence. This study was designed to investigate the association of MnSOD gene SNP (Val16Ala) with HCV and HCV-related HCC to elucidate its possible role in patho-genesis of HCC. The study included sixty individuals; they were classified into three groups; 20 patients with hepatitis C virus infection, 20 patients with hepatitis C virus-related HCC and 20 unrelated healthy volunteers who served as controls. Qualitative determination of Hepatitis C Virus antibody and quantitative determination of RNA-HCV by RT-PCR were done. MnSOD activity was evaluated using a superoxide dis-mutase assay kit. Genotyping was performed by polymerase chain reaction and re-striction fragment length polymorphism (PCR-RFLP) method. The homozygous Ala/Ala (CC) was significantly more frequent in HCV-related HCC patients com-pared to HCV-infected patients and control group (67.5%, 12%, and 15% respective-ly, p ˂ 0.05). Moreover, the C allele was more often associated with HCV-related HCC patients compared to HCV-infected patients and control group (50%, 10%, and 15% respectively, p ˂ 0.05). MnSOD activity was significantly higher in HCV-related HCC patients and HCV-infected patients compared to control group (185.6± 49.3, 142.6± 27.3 and 66.25± 17.03 respectively, p ˂ 0.05). In addition, MnSOD ac-tivity was significantly higher with CC and TC genotypes than TT genotypes in all HCV-infected patients with/without HCC (p < 0.05). There is increased susceptibility to HCC among HCV-infected patients with MnSOD gene SNP (Val16Ala). Serum MnSOD level was increased as HCV-related chronic liver disease progressed, espe-cially among patients with HCC.
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