Do Genetic Variations in Antioxidant Enzymes Influence the Course of Hereditary Hemochromatosis?

Iron-induced oxidative stress promotes hepatic injury in hereditary hemochromatosis, which can be influenced by genetic traits affecting antioxidant enzymes. We assessed the influence of Ala16Val-superoxide dismutase 2, Pro198Leu-glutathione peroxidase 1, and -463G/A-myeloperoxidase genotypes (high activity for the Ala, Pro, and G alleles, respectively) on the risks of cirrhosis and hepatocellular carcinoma (HCC) in patients homozygous for the C282Y-hemochromatosis (HFE) gene mutation. Both the 2G-myeloperoxidase genotype and carriage of one or two copies of the Ala-superoxide dismutase 2 allele were more frequent in patients with cirrhosis or HCC. Patients cumulating these two genetic traits had higher rates of cirrhosis and HCC than other patients. Antioxid. Redox Signal. 15, 31-38.