Meng Haiying, Hou Yiping
School of Forensic and Pre-Clinical Medicine, Sichuan University, Chengdu, Sichuan, 610041 P. R. China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2002 Apr;19(2):159-62.
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.
HFE基因是一种主要组织相容性复合体I类样基因，于1996年被鉴定为血色素沉着症的候选基因。HFE的推测作用是其参与调节转铁蛋白受体与转铁蛋白之间的相互作用。血色素沉着症是常见的常染色体隐性铁过载疾病，至少每300名白种人中就有1人受其影响。HFE基因中C282Y突变的鉴定引发了人群筛查研究。这项工作大多还包括对另一种突变H63D的分析，该突变似乎具有低外显率。最近发现HFE蛋白可与转铁蛋白受体共沉淀，并影响转铁蛋白与转铁蛋白受体之间的反应。功能数据表明，C282Y突变消除了HFE蛋白与β2-微球蛋白（β2M）的结合，使得该复合体无法到达细胞表面。显然，如果突变蛋白无法到达细胞表面，这种调节特性就会缺失。HFE基因中另一种突变H63D的作用尚不清楚。目前的数据表明，这种突变蛋白可与β2-微球蛋白结合并确实能到达细胞表面，缺陷在于未能改变转铁蛋白受体对转铁蛋白的亲和力。这无法解释与该突变相关的低外显率程度。
