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-1αPro-582-Ser variant is associated with elevated transactivation capacity of hypoxia responsive elements of target genes, we investigated whether the HIF-1αPro-582-Ser polymorphism might influence the response to repeated blood withdrawals. Materials and methods. Using polymerase chain reaction analysis and DNA sequencing, we retrospectively investigated the presence of HIF- 1αPro-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-1αPro-582-Ser polymorphism had higher haemoglobin and ferritin levels than individuals homozygous for the wild-type allele. Moreover, the HIF-1αPro-582-Serpolymorphism protected regular blood donors from developing iron deficiency and anaemia and predicted uninterrupted donation activity. Discussion. These findings show for the first time that the HIF-1αPro-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-1αPro-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. © SIMTI Servizi Srl.

Hypoxia-inducible factor-1α(Pro-582-Ser) polymorphism prevents iron deprivation in healthy blood donors / Torti, L.; Teofili, L.; Capodimonti, S.; Nuzzolo, E. R.; Iachininoto, M. G.; Massini, G.; Coluzzi, S.; Tafuri, Agostino; Fiorin, F.; Girelli, Gabriella; Zini, G.; Larocca, L. M.. - In: BLOOD TRANSFUSION. - ISSN 1723-2007. - STAMPA. - 11:4(2013), pp. 553-557. [10.2450/2013.0076-13]

Hypoxia-inducible factor-1α(Pro-582-Ser) polymorphism prevents iron deprivation in healthy blood donors.

S. Coluzzi;TAFURI, Agostino;GIRELLI, Gabriella;
2013

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-1αPro-582-Ser variant is associated with elevated transactivation capacity of hypoxia responsive elements of target genes, we investigated whether the HIF-1αPro-582-Ser polymorphism might influence the response to repeated blood withdrawals. Materials and methods. Using polymerase chain reaction analysis and DNA sequencing, we retrospectively investigated the presence of HIF- 1αPro-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-1αPro-582-Ser polymorphism had higher haemoglobin and ferritin levels than individuals homozygous for the wild-type allele. Moreover, the HIF-1αPro-582-Serpolymorphism protected regular blood donors from developing iron deficiency and anaemia and predicted uninterrupted donation activity. Discussion. These findings show for the first time that the HIF-1αPro-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-1αPro-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. © SIMTI Servizi Srl.
2013
gene; hif1a; hypoxia-inducible factor; blood donors; polycythemia; thrombocythemia; iron deficiency
01 Pubblicazione su rivista::01a Articolo in rivista
Hypoxia-inducible factor-1α(Pro-582-Ser) polymorphism prevents iron deprivation in healthy blood donors / Torti, L.; Teofili, L.; Capodimonti, S.; Nuzzolo, E. R.; Iachininoto, M. G.; Massini, G.; Coluzzi, S.; Tafuri, Agostino; Fiorin, F.; Girelli, Gabriella; Zini, G.; Larocca, L. M.. - In: BLOOD TRANSFUSION. - ISSN 1723-2007. - STAMPA. - 11:4(2013), pp. 553-557. [10.2450/2013.0076-13]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/558584
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