The haptoglobin 2-2 phenotype affects serum markers of iron status in healthy males

Background: Human iron status is influenced by environmental and genetic fa ctors. We hypothesized that the genetic polymorphism of haptoglobin (Hp), a hemoglobin-binding plasma protein, could affect iron status. Methods: Reference values of serum iron status markers were compared accord ing to Hp phenotypes (Hp 1-1, Hp 2-1, Hp 2-2; determined by starch gel elec trophoresis) in 717 healthy adults. Iron storage was investigated in periph eral blood monocyte-macrophages by measuring cytosolic L- and H-ferritins a nd by in vitro uptake of radiolabeled (I-125) hemoglobin-haptoglobin comple xes. Results: In males but not in females, the Hp 2-2 phenotype was associated w ith higher serum iron (P <0.05), transferrin saturation (P <0.05), and ferr itin (P <0.01) concentrations than Hp 1-1 and 2-1, whereas soluble transfer rin receptor concentrations were lower (P <0.05). Moreover, serum ferritin correlated with monocyte L-ferritin content (r = 0.699), which was also hig hest in the male Hp 2-2 subgroup (P <0.01). In vitro, monocyte-macrophages took up a small fraction of I-125-labeled hemoglobin complexed to Hp 2-2 bu t not to Hp 1-1 or 2-1. Conclusions: The Hp 2-2 phenotype affects serum iron status markers in heal thy males and is associated with higher L-ferritin concentrations in monocy te-macrophages because of a yet undescribed iron delocalization pathway, se lectively occurring in Hp 2-2 subjects. (C) 2000 American Association for C linical Chemistry.