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Cited by 198Iron Metabolism and DisordersNeurological diseases and metabolismHemoglobinopathies and Related Disorders

Iron overload in Africans and African-Americans and a common mutation in the SCL40A1 (ferroportin 1) gene☆

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Gordeuk, Victor R, Caleffi, Angela, Corradini, Elena, Ferrara, Francesca, Jones, Russell A, Castro, Oswaldo, Onyekwere, Onyinye, Kittles, Rick +9 more·2003·Blood Cells, Molecules, and Diseases
DOI 10.1016/s1079-9796(03)00164-5
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Abstract

The product of the SLC40A1 gene, ferroportin 1, is a main iron export protein. Pathogenic mutations in ferroportin 1 lead to an autosomal dominant hereditary iron overload syndrome characterized by high serum ferritin concentration, normal transferrin saturation, iron accumulation predominantly in macrophages, and marginal anemia. Iron overload occurs in both the African and the African-American populations, but a possible genetic basis has not been established. We analyzed the ferroportin 1 gene in 19 unrelated patients from southern Africa (N = 15) and the United States (N = 4) presenting with primary iron overload. We found a new c. 744 C-->T (Q248H) mutation in the SLC40A1 gene in 4 of these patients (3 Africans and 1 African-American). Among 22 first degree family members, 10 of whom were Q248H heterozygotes, the mutation was associated with a trend to higher serum ferritin to amino aspartate transferase ratios (means of 14.8 versus 4.3 microg/U; P = 0.1) and lower hemoglobin concentrations (means of 11.8 versus 13.2 g/dL; P = 0.1). The ratio corrects serum ferritin concentration for alcohol-induced hepatocellular damage. We also found heterozygosity for the Q248H mutation in 7 of 51 (14%) southern African community control participants selected because they had a serum ferritin concentration below 400 microg/L and in 5 of 100 (5%) anonymous African-Americans, but we did not find the change in 300 Caucasians with normal iron status and 25 Caucasians with non-HFE iron overload. The hemoglobin concentration was significantly lower in the African community controls with the Q248H mutation than in those without it. We conclude that the Q248H mutation is a common polymorphism in the ferroportin 1 gene in African populations that may be associated with mild anemia and a tendency to iron loading.

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  • An endemic form of secondary iron overload is linked to a mutation in the ferroportin gene.

    “An endemic form of secondary iron overload has been linked to a mutation in the ferroportin gene (186) and is associated with an increased incidence and mortality from TB.”

    From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [186]

  • This endemic secondary iron overload is associated with increased incidence and mortality from TB.

    “An endemic form of secondary iron overload has been linked to a mutation in the ferroportin gene (186) and is associated with an increased incidence and mortality from TB.”

    From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [186]

  • Individuals carrying mutations in the FPN gene, associated with intracellular iron retention and secondary siderosis in Africa (Bantu disease), have increased incidence of Mycobacteria infection and higher mortality from tuberculosis.

    “The pathophysiologic relevance of this mechanism is illustrated by the fact that individuals carrying mutations in the FPN gene, which is associated with intracellular Fe retention and secondary siderosis in Africa (also termed Bantu disease), are challenged with an increased incidence of Mycobacteria infection and higher mortality from tuberculosis [162].”

    From The Iron age of host–microbe interactions (2015) · cites this paper as [162]

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Authors
Gordeuk, V. R., Caleffi, A., Corradini, E., Ferrara, F., Jones, R. A., Castro, O., Onyekwere, O., Kittles, R., Pignatti, E., Montosi, G., Garuti, C., Gangaidzo, I. T., Gomo, Z. A. R., Moyo, V. M., Rouault, T. A., MacPhail, P., & Pietrangelo, A.
Affiliations
  • Howard University (US)
  • University of Modena and Reggio Emilia (IT)
  • University of Zimbabwe (ZW)
  • University of Connecticut (US)
  • National Institutes of Health (US)
  • University of the Witwatersrand (ZA)
Corresponding author
Pietrangelo, Antonello
ORCID
Venue
Blood Cells, Molecules, and Diseases
Publisher
Elsevier BV
Published
2003-11
Volume
31
Issue
3
Pages
299-304
ISSN
1079-9796 (ISSN-L)
DOI
10.1016/s1079-9796(03)00164-5
OpenAlex
W2057358785
Cited by
198
References
18
Citations by year
2026: 1 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 8 · 2020: 5 · 2019: 3 · 2018: 8 · 2017: 6 · 2016: 8 · 2015: 5 · 2014: 5 · 2013: 6 · 2012: 8
FWCI
9.91
Type
journal article
Language
en
Update notices
erratum (2004-07-01)
Open access
Licence
Locations
  • Blood Cells Molecules and Diseases (publishedVersion)
  • PubMed (publishedVersion)
  • IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
Funders
  • National Heart, Lung, and Blood Institute (UH1-HL03679-05, UH1HL003679)
  • National Center for Research Resources (M01RR010284, M01-RR10284)
Topics
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
  • Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
Keywords
iron overload, ferroportin 1, SLC40A1, hereditary iron overload, serum ferritin, hemoglobin, anemia, African populations, African Americans, genetic polymorphism, Southern Africa
MeSH terms
Ferroportin, Base Sequence, Black or African American, Female, Ferritins, Glutamine, Hematologic Tests, Histidine, Humans, Iron, Middle Aged, Molecular Sequence Data, Mutation, Polymorphism, Genetic, Iron Overload, Cation Transport Proteins, Black People

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