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Clinical Chemistry 46: 1619-1625, 2000;
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(Clinical Chemistry. 2000;46:1619-1625.)
© 2000 American Association for Clinical Chemistry, Inc.

Articles

The Haptoglobin 2-2 Phenotype Affects Serum Markers of Iron Status in Healthy Males

Michel R. Langlois1,a, Marie-Elise Martin2, Johan R. Boelaert3, Carole Beaumont2, Youri E. Taes1, Marc L. De Buyzere1, Dirk R. Bernard3, Hugo M. Neels4 and Joris R. Delanghe1

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.




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