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1
Department of Clinical Chemistry, Immunology and Microbiology, University Hospital Gent, De Pintelaan 185, B-9000 Gent, Belgium.
2
Génétique et Pathologie Moléculaire de
l’Hématopoièse, INSERM U409, Faculté Xavier Bichat,
16 rue Henri Huchard, BP416, 75870 Paris Cedex 18, France.
3
Unit for Renal and Infectious Diseases and Laboratory of
Clinical Chemistry, General Hospital St.-Jan, Ruddershove 10, B-8000
Brugge, Belgium.
4
Laboratory of Clinical Chemistry, General Hospital
Middelheim, Lindendreef 1, B-2020 Antwerpen, Belgium.
a Address correspondence to: Laboratory of Clinical Chemistry, University Hospital Gent, De Pintelaan 185, B-9000 Gent, Belgium. Fax 32-9-2404985; e-mail michel.langlois{at}rug.ac.be
Background: 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.
Methods: 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 (125I) hemoglobin-haptoglobin complexes.
Results: 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 125I-labeled hemoglobin complexed to Hp 2-2 but not to Hp 1-1 or 2-1.
Conclusions: 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.
The following articles in journals at HighWire Press have cited this article:
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 S. Fagoonee, J. Gburek, E. Hirsch, S. Marro, S. K. Moestrup, J. M. Laurberg, E. I. Christensen, L. Silengo, F. Altruda, and E. Tolosano Plasma Protein Haptoglobin Modulates Renal Iron Loading Am. J. Pathol., April 1, 2005; 166(4): 973 - 983. [Abstract] [Full Text] [PDF]
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 A. P. Levy, P. Friedenberg, R. Lotan, P. Ouyang, M. Tripputi, L. Higginson, F. R. Cobb, J.-C. Tardif, V. Bittner, and B. V. Howard The Effect of Vitamin Therapy on the Progression of Coronary Artery Atherosclerosis Varies by Haptoglobin Type in Postmenopausal Women Diabetes Care, April 1, 2004; 27(4): 925 - 930. [Abstract] [Full Text] [PDF]
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H. Van Vlierberghe and J. Delanghe Haptoglobin Polymorphism and Iron Hemostasis Clin. Chem., April 1, 2003; 49(4): 708 - 709. [Full Text] [PDF]
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E. Beutler, T. Gelbart, and P. Lee Haptoglobin Polymorphism and Iron Homeostasis Clin. Chem., December 1, 2002; 48(12): 2232 - 2235. [Abstract] [Full Text] [PDF]
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