Discovery of the main genes regulating iron metabolism is the result of the study of hemochromatosis

Abstract

The review article is devoted to the history of the discovery of genes that regulate iron metabolism. The natural model that became the basis for the study of genes was hemochromatosis (HC). HC is a hereditary disease caused by excess iron in tissues. The first to be discovered was the HFE gene, whose physiological role is to prevent iron overload in cells by decreasing the binding of transferrin receptor-1 (TFR-1) to metal-saturated transferrin. This happened in 1996; the gene was mapped to chromosome 6p.23.3. In the European population, mutations in the HFE gene were detected in 80-100% of patients with HC. This variant of the disease is classified as type 1 He in OMIM. In 1999, the HJV gene on chromosome 1q21 was discovered, the product of which, hemouvelin, was later found to modulate the expression of hepcidin, and the SLC40A1 gene on chromosome 2q32, which encodes ferroportin, an iron transporter from enterocytes, macrophages, hepatocytes and placental cells into blood plasma. HC associated with mutations in these genes is represented by types 2A and 4 in the OMIM classification. In 2000, the HAMP gene on chromosome 19q13.1 was discovered, encoding the main iron regulatory hormone hepcidin, which blocks ferroportin, and the TFR-2 gene on chromosome 7q22. controlling the capture of iron by hepato-cytes and bone marrow cells, as well as the level of metal in the blood plasma. HC associated with mutations in these genes is represented by types 2B and 3 in the OMIM classification.