TMPRSS6 genotype has been shown to influence iron metabolism in animal models of hereditary hemochromatosis and beta-thalassemia [50], [51], but the effect on iron overload in patients with hemochromatosis is still controversial [43], and no data were available for the effect of TMPRSS6 genotype in models of iron overload where hepcidin upregulation is preserved 15,33. This evidence concerns the gene TMPRSS6 and hereditary hemochromatosis.