Association of Catalase and Glutathione Peroxidase 1 Polymorphisms with Chronic Hepatitis C Outcome

• Published in: Annals of human genetics Vol. 80; no. 3; pp. 145 - 153
• Main Authors: Sousa, Vanessa C.S.D., Carmo, Rodrigo F., Vasconcelos, Luydson R.S., Aroucha, Dayse C.B.L., Pereira, Leila M.M.B., Moura, Patrícia, Cavalcanti, Maria S.M.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.05.2016
• Subjects: Adult; Aged; Alleles; Carcinoma, Hepatocellular - genetics; CAT; Catalase - genetics; Female; Gene Frequency; Genotype; Glutathione Peroxidase - genetics; Glutathione Peroxidase GPX1; GPX1; HCC; HCV; Hepatitis; Hepatitis C virus; Hepatitis C, Chronic - genetics; Humans; Liver cirrhosis; Liver Cirrhosis - genetics; Liver Neoplasms - genetics; Male; Middle Aged; Polymorphism, Single Nucleotide; Risk Factors; ROS; HCC; HCV; GPX1; CAT; ROS
• ISSN: 0003-4800; 1469-1809
• DOI: 10.1111/ahg.12152

Summary The hepatic damage caused by hepatitis C virus (HCV) infection is associated with the host immune response and viral regulatory factors. Catalase (CAT) and glutathione peroxidase 1 (GPX1) are antioxidant enzymes located in the peroxisomes and mitochondria, respectively, and are responsible for the control of intracellular hydrogen peroxide levels. Polymorphisms in CAT (C‐262T) and GPX1 (Pro198Leu) are correlated with serum levels and enzyme activity. This study aimed to investigate the association of genetic polymorphisms of CAT C‐262T (rs1001179) and GPX1 Pro198Leu (rs1050450) with different stages of liver fibrosis and development of hepatocellular carcinoma (HCC). This study included 445 patients with chronic hepatitis C, of whom 139 patients had mild fibrosis (F0‐F1), 200 had moderate/severe fibrosis (F2‐F4), and 106 had HCC. Genotyping of SNPs was performed by real‐time PCR using TaqMan probes. The Pro/Pro genotype of GPX1 was significantly associated with fibrosis severity, HCC, Child Pugh score, and BCLC staging. Additionally, patients carrying both CT+TT genotypes in the CAT gene and the Pro/Pro genotype in the GPX1 gene had higher risk for developing moderate/severe fibrosis or HCC (p = 0.009, OR 2.40 and p = 0.002, OR 3.56, respectively). CAT and GPX1 polymorphisms may be implicated in the severity of liver fibrosis and HCC caused by HCV.