The haptoglobin 2-2 phenotype affects serum markers of iron status in healthy males.
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 ((125)I) 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 (125)I-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.
Langlois
M R
MR
Department of Clinical Chemistry, Immunology and Microbiology, University Hospital Gent, De Pintelaan 185, B-9000 Gent, Belgium. michel.langlois@rug.ac.be
Martin
M E
ME
Boelaert
J R
JR
Beaumont
C
C
Taes
Y E
YE
De Buyzere
M L
ML
Bernard
D R
DR
Neels
H M
HM
Delanghe
J R
JR
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D003600:Cytosol / Q000737:chemistry; D004592:Electrophoresis, Starch Gel; D005260:Female; D005293:Ferritins / Q000032:analysis; D006242:Haptoglobins / Q000235:genetics*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism*; D008264:Macrophages / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry / Q000378:metabolism; D010641:Phenotype; D011110:Polymorphism, Genetic; D011990:Receptors, Transferrin / Q000032:analysis; D012016:Reference Values; D014168:Transferrin / Q000032:analysis
D015415:Biomarkers; D006242:Haptoglobins; D006454:Hemoglobins; D011990:Receptors, Transferrin; D014168:Transferrin; D005293:Ferritins; D007501:Iron