title: Hypoxia-inducible factor-1α(Pro-582-Ser) polymorphism prevents iron deprivation in healthy blood donors.
abstract: BACKGROUND
  Frequent blood loss induces progressive depletion of iron stores, leading to iron deficiency and, ultimately, to overt iron-deficient anaemia. The erythropoietin-mediated bone marrow response to anaemia is under the control of hypoxia-inducible factors (HIF), the master regulators of oxygen and iron homeostasis. Since the HIF-1α(Pro-582-Ser) variant is associated with elevated trans-activation capacity of hypoxia responsive elements of target genes, we investigated whether the HIF-1α(Pro-582-Ser) polymorphism might influence the response to repeated blood withdrawals.
  
  
  METHODS
  Using polymerase chain reaction analysis and DNA sequencing, we retrospectively investigated the presence of HIF-1α(Pro-582-Ser) in a series of 163 blood donors. Haematological findings, serum ferritin levels and frequency of donations were compared according to the mutational status of the HIF-1α gene.
  
  
  RESULTS
  We found that male carriers of the HIF-1α(Pro-582-Ser) polymorphism had higher haemoglobin and ferritin levels than individuals homozygous for the wild-type allele. Moreover, the HIF-1α(Pro-582-Ser) polymorphism protected regular blood donors from developing iron deficiency and anaemia and predicted uninterrupted donation activity.
  
  
  CONCLUSIONS
  These findings show for the first time that the HIF-1α(Pro-582-Ser) polymorphism significantly affects red blood cell and iron homeostasis after blood loss, conferring to male carriers a resistance to anaemia. Regarding the female gender, large series of individuals should be investigated to establish whether there is an effect of the HIF-1α(Pro-582-Ser) polymorphism in this population. Although these data need to be confirmed in prospective studies, they could have important implications in blood donor selection and donation procedures.
authors.affiliation: Institute of Haematology, "Sacred Heart" Catholic University, Rome, Italy Transfusion Centre of Jesolo, Portogruaro and San Donà di Piave Hospitals, San Donà di Piave, Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Torti
authors.affiliation: Institute of Haematology, "Sacred Heart" Catholic University, Rome, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Teofili
authors.affiliation: Institute of Haematology, "Sacred Heart" Catholic University, Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Capodimonti
authors.affiliation: Institute of Haematology, "Sacred Heart" Catholic University, Rome, Italy.
authors.forename: Eugenia R
authors.initials: ER
authors.lastname: Nuzzolo
authors.affiliation: Institute of Haematology, "Sacred Heart" Catholic University, Rome, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Iachininoto
authors.affiliation: Institute of Haematology, "Sacred Heart" Catholic University, Rome, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Massini
authors.affiliation: Department of Molecular Medicine, Institute of Haematology, "Sapienza" University, Rome, Italy.
authors.forename: Serelina
authors.initials: S
authors.lastname: Coluzzi
authors.affiliation: Department of Molecular Medicine, Institute of Haematology, "Sapienza" University, Rome, Italy.
authors.forename: Agostino
authors.initials: A
authors.lastname: Tafuri
authors.affiliation: Transfusion Centre of Jesolo, Portogruaro and San Donà di Piave Hospitals, San Donà di Piave, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Fiorin
authors.affiliation: Department of Molecular Medicine, Institute of Haematology, "Sapienza" University, Rome, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Girelli
authors.affiliation: Institute of Haematology, "Sacred Heart" Catholic University, Rome, Italy.
authors.forename: Gina
authors.initials: G
authors.lastname: Zini
authors.affiliation: Institute of Pathological Anatomy, "Sacred Heart" Catholic University, Rome, Italy.
authors.forename: Luigi M
authors.initials: LM
authors.lastname: Larocca
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000097:blood / Q000209:etiology / Q000235:genetics; D001782:Blood Donors; D046148:Donor Selection; D005260:Female; D005293:Ferritins / Q000097:blood* / Q000235:genetics; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D007501:Iron / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA / Q000379:methods; D012727:Sex Characteristics
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D005293:Ferritins; D007501:Iron