title: Hepcidin is suppressed by erythropoiesis in hemoglobin E β-thalassemia and β-thalassemia trait.
abstract: Hemoglobin E (HbE) β-thalassemia is the most common severe thalassemia syndrome across Asia, and millions of people are carriers. Clinical heterogeneity in HbE β-thalassemia is incompletely explained by genotype, and the interaction of phenotypic variation with hepcidin is unknown. The effect of thalassemia carriage on hepcidin is also unknown, but it could be relevant for iron supplementation programs aimed at combating anemia. In 62 of 69 Sri Lankan patients with HbE β-thalassemia with moderate or severe phenotype, hepcidin was suppressed, and overall hepcidin inversely correlated with iron accumulation. On segregating by phenotype, there were no differences in hepcidin, erythropoiesis, or hemoglobin between severe or moderate disease, but multiple linear regression showed that erythropoiesis inversely correlated with hepcidin only in severe phenotypes. In moderate disease, no independent predictors of hepcidin were identifiable; nevertheless, the low hepcidin levels indicate a significant risk for iron overload. In a population survey of Sri Lankan schoolchildren, β-thalassemia (but not HbE) trait was associated with increased erythropoiesis and mildly suppressed hepcidin, suggesting an enhanced propensity to accumulate iron. In summary, the influence of erythropoiesis on hepcidin suppression associates with phenotypic disease variation and pathogenesis in HbE β-thalassemia and indicates that the epidemiology of β-thalassemia trait requires consideration when planning public health iron interventions.
authors.affiliation: Medical Research Council, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom;
authors.forename: Emma
authors.initials: E
authors.lastname: Jones
authors.affiliation: Medical Research Council, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom;
authors.forename: Sant-Rayn
authors.initials: SR
authors.lastname: Pasricha
authors.affiliation: College of Medicine, Swansea University, Swansea, United Kingdom;
authors.forename: Angela
authors.initials: A
authors.lastname: Allen
authors.affiliation: University College of London Cancer Institute, Department of Haematology, University College London, United Kingdom;
authors.forename: Patricia
authors.initials: P
authors.lastname: Evans
authors.affiliation: Medical Research Council, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom;
authors.forename: Chris A
authors.initials: CA
authors.lastname: Fisher
authors.affiliation: Medical Research Council, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom;
authors.forename: Katherine
authors.initials: K
authors.lastname: Wray
authors.affiliation: University of Kelaniya, Colombo, Sri Lanka;
authors.forename: Anuja
authors.initials: A
authors.lastname: Premawardhena
authors.affiliation: National Thalassaemia Centre, District Hospital, Kurunegala, Sri Lanka;
authors.forename: Dyananda
authors.initials: D
authors.lastname: Bandara
authors.affiliation: National Thalassaemia Centre, District Hospital, Kurunegala, Sri Lanka;
authors.forename: Ashok
authors.initials: A
authors.lastname: Perera
authors.affiliation: Department of Biochemistry and Immunology, Birmingham Heartlands Hospital, Birmingham, United Kingdom;
authors.forename: Craig
authors.initials: C
authors.lastname: Webster
authors.affiliation: Department of Biochemistry and Immunology, Birmingham Heartlands Hospital, Birmingham, United Kingdom;
authors.forename: Pamela
authors.initials: P
authors.lastname: Sturges
authors.affiliation: University Health Network, University of Toronto, ON, Canada; and.
authors.forename: Nancy F
authors.initials: NF
authors.lastname: Olivieri
authors.affiliation: School of Physics, University of Western Australia, Crawley, Australia.
authors.forename: Timothy
authors.initials: T
authors.lastname: St Pierre
authors.affiliation: Medical Research Council, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom;
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Armitage
authors.affiliation: University College of London Cancer Institute, Department of Haematology, University College London, United Kingdom;
authors.forename: John B
authors.initials: JB
authors.lastname: Porter
authors.affiliation: Medical Research Council, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom;
authors.forename: David J
authors.initials: DJ
authors.lastname: Weatherall
authors.affiliation: Medical Research Council, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom;
authors.forename: Hal
authors.initials: H
authors.lastname: Drakesmith
mesh_terms: D000293:Adolescent; D000328:Adult; D002353:Carrier State; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004920:Erythropoiesis / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006446:Hemoglobin E / Q000235:genetics* / Q000378:metabolism; D064451:Hepcidins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism; D019190:Iron Overload / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D012720:Severity of Illness Index; D013188:Sri Lanka; D065227:Transfusion Reaction; D055544:beta-Globins / Q000235:genetics* / Q000378:metabolism; D017086:beta-Thalassemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy
chemical_list: C578702:HAMP protein, human; D064451:Hepcidins; D055544:beta-Globins; D006446:Hemoglobin E; D007501:Iron