The aim of this study was to elucidate the role of polymorphisms in genes that encode FPN and matriptase-2 in the modulation of iron balance in the body by observing biochemical parameters in individuals with mild-to-severe iron overload, not due to genetic hemochromatosis, metabolic diseases, transfusion-dependent pathologies, or xenobiotic factors. This evidence concerns the gene SLC40A1 and Tangier disease.