title: Behavioral, biochemical, and genetic analysis of iron metabolism in high-intensity blood donors.
abstract: BACKGROUND
  Individuals donating whole blood 13 times in a 2-year period without development of iron deficiency anemia (superdonors) are a self-selected population that is deferred for low hematocrit (Hct) level less frequently than other donors.
  
  
  METHODS
  Iron metabolism was assessed in 138 superdonors through a questionnaire and measurement of Hct, serum ferritin, serum hepcidin, and serum growth differentiation factor 15 (GDF15). Genetic testing for HFE and JAK-2 mutations was also performed.
  
  
  CONCLUSIONS
  Iron deficiency (ferritin level, <30 microg/L) is present in more than 60 percent of superdonors. Behaviors altering iron status included casual use of iron supplements in males, but not in females, and cigarette smoking that produced increased Hct associated with decreased ferritin. The striking biochemical characteristic of superdonors is greatly decreased serum hepcidin, consistent with their need to absorb maximal amounts of dietary iron to replace that lost from blood donation. GDF15 is normal in most superdonors, indicating that GDF15 overexpression arising from the expanded erythroid pool necessary to replace donated red cells is not the biochemical mechanism for the decreased serum hepcidin. Mutations in JAK-2 were not found, indicating that undiagnosed polycythemia vera is not a common cause for successful repeated blood donation by superdonors. Mutations in HFE associated with hemochromatosis were present in superdonors at the same frequency as the normal population. However, superdonors heterozygous for the H63D mutation in HFE had significantly decreased hepcidin : ferritin ratios demonstrating for the first time that the heterozygous state for HFE mutations is associated with alterations in hepcidin expression.
authors.affiliation: Blood Research Institute, Blood Center of Wisconsin, Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin 53226-3548, USA. alan.mast@bcw.edu
authors.forename: Alan E
authors.initials: AE
authors.lastname: Mast
authors.forename: Tisha M
authors.initials: TM
authors.lastname: Foster
authors.forename: Holly L
authors.initials: HL
authors.lastname: Pinder
authors.forename: Craig A
authors.initials: CA
authors.lastname: Beczkiewicz
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Bellissimo
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Murphy
authors.forename: Steve
authors.initials: S
authors.lastname: Kovacevic
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Wroblewski
authors.forename: Derrick R
authors.initials: DR
authors.lastname: Witcher
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000097:blood* / Q000188:drug therapy / Q000235:genetics*; D023181:Antimicrobial Cationic Peptides / Q000097:blood; D001782:Blood Donors; D016207:Cytokines / Q000235:genetics*; D005260:Female; D005293:Ferritins / Q000097:blood; D055436:Growth Differentiation Factor 15; D006400:Hematocrit; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000494:pharmacology; D019266:Iron, Dietary / Q000494:pharmacology; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D011087:Polycythemia Vera / Q000235:genetics; D012907:Smoking / Q000097:blood; D011795:Surveys and Questionnaires
chemical_list: D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; C578702:HAMP protein, human; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; D019266:Iron, Dietary; D008565:Membrane Proteins; D005293:Ferritins; D007501:Iron; C507924:JAK2 protein, human; D053614:Janus Kinase 2