Gottschalk R, Seidl C, Schilling S, Braner A, Seifried E, Hoelzer D, Kaltwasser J P
Department of Internal Medicine III, J-W Goethe University, Frankfurt/ Main, Germany.
Eur J Immunogenet. 2000 Jun;27(3):129-34. doi: 10.1046/j.1365-2370.2000.00215.x.
Gene variations of HFE, a HLA-class I like molecule, are highly associated with hereditary haemochromatosis (HH). Functional as well as molecular studies of the HFE protein have indicated that the molecule is involved in iron metabolism and that the HFE gene variations observed among HH patients affect its interaction with the transferrin receptor (TfR). In the present study, we have therefore analysed the relationship between the HFE gene variants, C282Y and H63D, and body iron status among 85 German HH patients. In addition, two TfR gene polymorphism, TfR-Hin6I and TfR-BanI, were typed that have been reported to define ethnically distinct haplotypes. As controls we used 251/159 healthy German blood donors. Seventy-eight (92%) patients were C292Y homozygous, the H63D mutation was present in five (6%) patients with none of the patients being H63D homozygous. Serum transferrin, transferrin saturation and liver iron content were determined prior to therapeutic intervention. Among C282Y homozygous patients serum ferritin levels (2294 +/- 3174 vs. 463 +/- 224 microg L-1, P < 0.0001) and transferrin saturation (86 +/- 18% vs. 62 +/- 25%, P = 0.048) were elevated significantly compared with C282Y and/or H63D heterozygous patients. In addition, the liver iron content (291 +/- 165 vs. 138 +/- 95 micromol g-1, P = 0.028) and liver iron index (6.4 +/- 2.8 vs. 3.2 +/- 2.3, P = 0.019) were increased among C282Y homozygotes compared with C282Y heterozygotes. In contrast, no difference was observed between patients and controls regarding the distribution of TfR-Hin6I and TfR-BanI alleles. These data indicate that the iron intake is higher among C282Y homozygous patients compared with C282Y heterozygous or C282Y/H63D compound heterozygous individuals and supports the functional role of the HFE protein in iron metabolism whereas the TfR gene variants seem to have no influence on iron uptake.
HFE是一种类似于I类组织相容性复合体（HLA）的分子，其基因变异与遗传性血色素沉着症（HH）高度相关。对HFE蛋白的功能及分子研究表明，该分子参与铁代谢，且在HH患者中观察到的HFE基因变异会影响其与转铁蛋白受体（TfR）的相互作用。因此，在本研究中，我们分析了85例德国HH患者中HFE基因变异C282Y和H63D与机体铁状态之间的关系。此外，还对两种TfR基因多态性TfR - Hin6I和TfR - BanI进行了分型，据报道这两种多态性可定义不同种族的单倍型。我们将251名/159名德国健康献血者作为对照。78例（92%）患者为C292Y纯合子，5例（6%）患者存在H63D突变，无患者为H63D纯合子。在进行治疗干预前测定血清转铁蛋白、转铁蛋白饱和度和肝脏铁含量。与C282Y和/或H63D杂合子患者相比，C282Y纯合子患者的血清铁蛋白水平（2294±3174 vs. 463±224 μg L-1，P < 0.0001）和转铁蛋白饱和度（86±18% vs. 62±25%，P = 0.048）显著升高。此外，与C282Y杂合子相比，C282Y纯合子的肝脏铁含量（291±165 vs. 138±95 μmol g-1，P = 0.028）和肝脏铁指数（6.4±2.8 vs. 3.2±2.3，P = 0.019）增加。相比之下，患者与对照在TfR - Hin6I和TfR - BanI等位基因分布上未观察到差异。这些数据表明，与C282Y杂合子或C282Y/H63D复合杂合个体相比，C282Y纯合子患者的铁摄入量更高，支持了HFE蛋白在铁代谢中的功能作用，而TfR基因变异似乎对铁摄取没有影响。
Zotero 插件