Deugnier Yves, Brissot Pierre, Loréal Olivier
Service des maladies du Foie, INSERM CIC 0203, Université de Rennes 1 and IFR 140, CHU Pontchaillou, 35033 Rennes, France.
J Hepatol. 2008;48 Suppl 1:S113-23. doi: 10.1016/j.jhep.2008.01.014. Epub 2008 Feb 5.
The cross-talk which has taken place in recent years between clinicians and scientists has resulted in a greater understanding of iron metabolism with the discovery of new iron-related genes including the hepcidin gene which plays a critical role in regulating systemic iron homeostasis. Consequently, the distinction between (a) genetic iron-overload disorders including haemochromatosis related to mutations in the HFE, hemojuvelin, transferrin receptor 2 and hepcidin genes and (b) non-haemochromatotic conditions related to mutations in the ferroportin, ceruloplasmin, transferrin and di-metal transporter 1 genes, and (c) acquired iron-overload syndromes has become easier. However, major challenges still remain which include our understanding of the regulation of hepcidin production, the identification of environmental and genetic modifiers of iron burden and organ damage in iron-overload syndromes, especially HFE haemochromatosis, indications regarding the new oral chelator, deferasirox, and the development of new therapeutic tools interacting with the regulation of iron metabolism.
近年来临床医生与科学家之间的交流,使人们对铁代谢有了更深入的了解,发现了包括在调节全身铁稳态中起关键作用的铁调素基因在内的新的铁相关基因。因此,区分(a)遗传性铁过载疾病,包括与HFE、血色素沉着蛋白、转铁蛋白受体2和铁调素基因突变相关的血色素沉着症;(b)与铁转运蛋白、铜蓝蛋白、转铁蛋白和双金属转运蛋白1基因突变相关的非血色素沉着症;以及(c)获得性铁过载综合征变得更加容易。然而,仍然存在重大挑战,包括我们对铁调素产生调节的理解、铁过载综合征(尤其是HFE血色素沉着症)中铁负荷和器官损伤的环境和基因修饰因子的识别、新型口服螯合剂地拉罗司的适应证,以及与铁代谢调节相互作用的新治疗工具的开发。