HFE基因与遗传性血色素沉着症

HFE基因发现于1996年，属于HLA I类样基因，是遗传性血色素沉着症侯选基因。HFE分子的功能可能是参与调节转铁蛋白与转铁蛋白受体间的相互作用。遗传性血色素沉着症是一种常染色体隐性遗传性铁异常沉积性疾病，高加索群体中发病率高，平均不到300人就有一个是该病患者。大量群体遗传学研究结果，提示HFE基因C282Y突变与遗传性血色素沉着症显著相关，HFE H63D突变对遗传性血色素沉着症影响较小。新近发现，HFE分子通过与转铁蛋白受体反应影响转铁蛋白与转铁蛋白受体间的相互作用，从而调节体内铁平衡。C282Y突变可使HFE分子不能与β2微球蛋白结合，不能转运到细胞表面，从而失去对转铁蛋白和转铁蛋白受体作用的调节功能。H63D突变影响功能的机理目前尚不清楚，现有研究提示H63D突变蛋白可与β2微球蛋白结合，并转过到细胞表面，突变对分子功能的影响可能也表现在不能调节转铁蛋白和转铁蛋白受体间的作用。

Relationship between HFE gene and hereditary hemochromatosis

HFE gene is a major histocompatibility complex class I-like gene, which was identified as a candidate gene for hemochromatosis in 1996. The proposed role for HFE is its part in the regulation of the interaction of the transferrin receptor with transferrin. Hemochromatosis, the common autosomal recessive disease of iron overload, affects at least 1 in 300 Caucasians. The identification of the C282Y mutation in the HFE gene has led to population screening studies. Much of this work has also included the analysis of a second mutation, H63D, which appears to have a low penetrability. HFE protein was recently found to coprecipitate with the transferrin receptor and to affect the reaction between transferrin and the transferrin receptor. Functional data suggest that the mutation C282Y abolishes the association of the HFE protein with beta 2-microglobulin (beta 2M), making the complex unable to reach the cell surface. Clearly, if the mutation protein is unable to reach the cell surface, this regulatory feature is missing. The role of a second mutation in the HFE gene, H63D, is less clear. Current data suggest that this mutation protein can associate with beta 2-microglobulin and does reach the cell surface and that the defect lies in a failure to modify the affinity of the transferrin receptor for transferrin. This does not explain the low degree of penetrability associated with this mutation.