Association of MnSOD Ala16Val genotype and activity with hepatocellular carcinoma risk in HCV-infected Egyptian patients

ABSTRACT

Hepatocellular carcinoma [HCC] is the most common primary malignant tumour of the liver. Chronic infection with hepatitis C virus [HCV] is a risk factor for HCC occurrence. HCV infection causes oxidative stress in hepatic cells through overproduction of reactive oxygen species [ROS] that cause carcinogenesis. Manganese superoxide dismutase [MnSOD] is an antioxidant enzyme that quenches free radicals. Ala16Val MnSOD polymorphism has been associated with cancer. It results from substitution of T to C at nucleotide 47 causing a change of valine to alanine on the 16th residue of 24-amino acid of mitochondrial-targeting sequence [MTS]of MnSOD. This work aimed to assess the relationship between MnSOD Ala16Val genotype and activity and HCC development in HCV-infected Egyptian patients. This study was conducted on 75 HCV-infected HCC patients, 24 asymptomatic HCV-infected patients and 58 healthy controls. Genotypes were determined by polymerase chain reaction/restriction fragment length polymorphism [PCR/RFLP] analysis. MnSOD activity was measured using a superoxide dismutase assay kit. The HCC group included 56 males and 19 females. The mean +/- standard deviation [SD] of their age was 53.3 +/- 1.85 years. The Ala/Ala genotype frequency in HCC patients [36.0%] was significantly higher than that in asymptomatic HCV-infected patients [12.5%, p= 0.029] and in the healthy controls [18.9%, p=0.031]. There was a significant difference between MnSOD activity in HCC patients and those in asymptomatic HCV-infected patients and healthy control [p=0.000]. Moreover, there was a highly significant increase in MnSOD activity in HCC patients with Ala/Ala and Val/Ala than in those with Val/Val genotypes [p=0.007]. There is an evidence of association between Ala16Val MnSOD polymorphism and HCC occurrence in HCV-infected Egyptian patients. Furthermore, serum MnSOD activity was significantly higher in those patients compared to control subjects: