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 HAMP and Beta-thalassemia.