Langlois M R, Martin M E, Boelaert J R, Beaumont C, Taes Y E, De Buyzere M L, Bernard D R, Neels H M, Delanghe J R
Department of Clinical Chemistry, Immunology and Microbiology, University Hospital Gent, De Pintelaan 185, B-9000 Gent, Belgium.
Clin Chem. 2000 Oct;46(10):1619-25.
Human iron status is influenced by environmental and genetic factors. We hypothesized that the genetic polymorphism of haptoglobin (Hp), a hemoglobin-binding plasma protein, could affect iron status.
Reference values of serum iron status markers were compared according to Hp phenotypes (Hp 1-1, Hp 2-1, Hp 2-2; determined by starch gel electrophoresis) in 717 healthy adults. Iron storage was investigated in peripheral blood monocyte-macrophages by measuring cytosolic L- and H-ferritins and by in vitro uptake of radiolabeled ((125)I) hemoglobin-haptoglobin complexes.
In males but not in females, the Hp 2-2 phenotype was associated with higher serum iron (P <0.05), transferrin saturation (P <0.05), and ferritin (P <0.01) concentrations than Hp 1-1 and 2-1, whereas soluble transferrin receptor concentrations were lower (P <0.05). Moreover, serum ferritin correlated with monocyte L-ferritin content (r = 0.699), which was also highest in the male Hp 2-2 subgroup (P <0.01). In vitro, monocyte-macrophages took up a small fraction of (125)I-labeled hemoglobin complexed to Hp 2-2 but not to Hp 1-1 or 2-1.
The Hp 2-2 phenotype affects serum iron status markers in healthy males and is associated with higher L-ferritin concentrations in monocyte-macrophages because of a yet undescribed iron delocalization pathway, selectively occurring in Hp 2-2 subjects.
人体铁状态受环境和遗传因素影响。我们推测，结合血红蛋白的血浆蛋白触珠蛋白（Hp）的基因多态性可能会影响铁状态。
在717名健康成年人中，根据触珠蛋白表型（Hp 1-1、Hp 2-1、Hp 2-2；通过淀粉凝胶电泳测定）比较血清铁状态标志物的参考值。通过测量细胞溶质L-和H-铁蛋白以及体外摄取放射性标记的（125）I血红蛋白-触珠蛋白复合物，对外周血单核细胞-巨噬细胞中的铁储存进行研究。
在男性而非女性中，与Hp 1-1和2-1相比，Hp 2-2表型与更高的血清铁（P<0.05）、转铁蛋白饱和度（P<0.05）和铁蛋白（P<0.01）浓度相关，而可溶性转铁蛋白受体浓度较低（P<0.05）。此外，血清铁蛋白与单核细胞L-铁蛋白含量相关（r = 0.699），在男性Hp 2-2亚组中也最高（P<0.01）。在体外，单核细胞-巨噬细胞摄取了一小部分与Hp 2-2复合的（125）I标记血红蛋白，但未摄取与Hp 1-1或2-1复合的血红蛋白。
Hp 2-2表型影响健康男性的血清铁状态标志物，并且由于尚未描述的铁离域途径，与单核细胞-巨噬细胞中更高的L-铁蛋白浓度相关，这种途径选择性地发生在Hp 2-2个体中。
