Therefore, based on the mechanism of action and regulation of hepcidin and the presence of an intermediate iron status phenotype in individuals carrying both SLC40A1 and TMPRSS6 SNPs, our results support the hypothesis that SLC40A1 and TMPRSS6 SNPs modulate iron homeostasis by acting in the opposite direction and preventing a severe iron overload. Here, SLC40A1 is linked to Tangier disease.