Stuart K A, Anderson G J, Frazer D M, Powell L W, McCullen M, Fletcher L M, Crawford D H G
Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Ipswich Road, Wooloongabba, 4102 Queensland, Australia.
Gut. 2003 Jul;52(7):953-9. doi: 10.1136/gut.52.7.953.
In HFE associated hereditary haemochromatosis, the duodenal enterocyte behaves as if iron deficient and previous reports have shown increased duodenal expression of divalent metal transporter 1 (DMT1) and iron regulated gene 1 (Ireg1) in affected subjects. In those studies, many patients had undergone venesection, which is a potent stimulus of iron absorption. Our study investigated duodenal expression of DMT1 (IRE and non-IRE), Ireg1, hephaestin, and duodenal cytochrome-b (Dyctb) in untreated C282Y homozygous haemochromatosis patients, iron deficient patients, and iron replete subjects.
Total RNA was extracted from duodenal biopsies and expression of the iron transport genes was assessed by ribonuclease protection assay.
Expression of DMT1 (IRE) and Ireg1 was increased 3-5-fold in iron deficient subjects compared with iron replete subjects. Duodenal expression of DMT1 (IRE) and Ireg1 was similar in haemochromatosis patients and iron replete subjects but in haemochromatosis patients with elevated serum ferritin concentrations, both DMT1 (IRE) and Ireg1 expression were inappropriately increased relative to serum ferritin concentration. Hephaestin and Dcytb levels were not upregulated in haemochromatosis. DMT1 (IRE) and Ireg1 levels showed significant inverse correlations with serum ferritin concentration in each group of patients.
These findings are consistent with DMT1 (IRE) and Ireg1 playing primary roles in the adaptive response to iron deficiency. Untreated haemochromatosis patients showed inappropriate increases in DMT1 (IRE) and Ireg1 expression for a given level of serum ferritin concentration, although the actual level of expression of these iron transport genes was not significantly different from that of normal subjects.
在与HFE相关的遗传性血色素沉着症中，十二指肠肠上皮细胞的表现就好像缺铁一样，先前的报告显示，受影响个体的十二指肠中二价金属转运体1（DMT1）和铁调节基因1（Ireg1）的表达增加。在那些研究中，许多患者已经接受了静脉放血，这是铁吸收的有力刺激因素。我们的研究调查了未经治疗的C282Y纯合血色素沉着症患者、缺铁患者和铁储备充足的受试者中DMT1（IRE和非IRE）、Ireg1、铁氧化还原蛋白和十二指肠细胞色素b（Dyctb）的十二指肠表达情况。
从十二指肠活检组织中提取总RNA，并通过核糖核酸酶保护试验评估铁转运基因的表达。
与铁储备充足的受试者相比，缺铁受试者中DMT1（IRE）和Ireg1的表达增加了3至5倍。血色素沉着症患者和铁储备充足的受试者中DMT1（IRE）和Ireg1的十二指肠表达相似，但在血清铁蛋白浓度升高的血色素沉着症患者中，相对于血清铁蛋白浓度，DMT1（IRE）和Ireg1的表达均不适当增加。血色素沉着症中铁氧化还原蛋白和Dcytb水平未上调。每组患者中DMT1（IRE）和Ireg1水平与血清铁蛋白浓度呈显著负相关。
这些发现与DMT1（IRE）和Ireg1在缺铁适应性反应中起主要作用一致。未经治疗的血色素沉着症患者在给定的血清铁蛋白浓度水平下，DMT1（IRE）和Ireg1表达出现不适当增加，尽管这些铁转运基因的实际表达水平与正常受试者无显著差异。
