Antioxidant enzymes gene polymorphisms and hepatocellular carcinoma in hepatitis C virus-infected Egyptian patients

Abstract

Oxidative stress is an imbalance between production and elimination of reactive metabolites of oxygen and nitrogen, in favor of their production leading to potential damage. During oxidative stress, biologically important molecules and cells can be damaged, and this can be significant in the pathogenesis of many diseases. Reactive oxygen species (ROS) and ROS-induced cytokines are known to trigger the apoptosis of some hepatocytes and therefore contribute to inflammation, regeneration, fibrogenesis, and carcinogenesis. The enzymes generally considered to be the frontline defense against ROS are catalase (CAT), the mitochondrial manganese superoxide dismutase (MnSOD), and glutathione peroxidase (GPX). Our aim in this work is to assess the possible association of the antioxidant enzyme polymorphisms of CAT (c.C-262T, rs1001179), MnSOD (p.Val16Ala, rs4880), and GPX1 (p.Pro 198 Leu, rs1050450) with the development of hepatocellular carcinoma (HCC) in a sample of hepatitis C virus (HCV)-infected Egyptian patients. Genetic polymorphisms were estimated in 40 HCC patients on top of HCV infection, 20 cirrhotic patients on top of HCV infection, and 20 healthy control individuals. Genetic polymorphisms of CAT (c.C-262T), MnSOD (p.Val16Ala), and GPX1 (p.Pro 198 Leu) were studied using PCR-RFLP technique. With regard to CAT enzyme polymorphism, the frequency of the CC was significantly higher in HCC and cirrhosis patients compared to the healthy control group (p = 0.000). The frequency of the C allele in the three studied groups did not show statistically significant difference (p = 0.081). Patients bearing CT + TT genotypes had 0.107-fold and 0.205-fold reduced risk of development of liver cirrhosis and HCC [p = 0.001, 95 % CI (0.025–0.459); p = 0.010, 95 % CI (0.058–0.721)], respectively, compared to those bearing CC genotype. With regard to the MnSOD, the Ala/Ala genotype was significantly higher in the HCC group and cirrhosis group than in control individuals (p = 0.001). Similar results were found regarding the frequency of the Ala allele in the three studied groups (p = 0.128). Patients bearing Ala/Ala genotype that had 2.8-fold and 1.8-fold increased the risk of development of liver cirrhosis and HCC [p = 0.001, 95 % CI (1.753–4.530); p = 0.001, 95 % CI (1.415–2.471)], respectively, compared to those bearing Val/Val + Val/Ala genotypes. With regard to GPX1 gene, the frequency of Pro/Leu genotype was significantly higher in the HCC and cirrhotic group compared to control group (p = 0.000). There was a significant increase in Leu allelic frequency in HCC and cirrhotic patients than in control group (p = 0.006). The presence of Leu allele increased the risk of development of liver cirrhosis and, consequently, HCC by 3.7-fold [p = 0.018, 95 % CI (1.205–11.78)] and 4.9-fold [p = 0.001, 95 % CI (1.742–13.86)], respectively, compared to Pro allele. The presence of CC of CAT (c.C-262T), Ala/Ala of MnSOD (p.Val16Ala) genes, and Leu allele of GPX1 (Pro 198 Leu) gene is considered as risk factors for development of liver cirrhosis and HCC in the presence of HCV infection.