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

Victor R. Gordeuk, Angela Caleffi, Elena Corradini, Francesca Ferrara, Russell A. Jones, Oswaldo Castro, Onyinye Onyekwere, Rick A Kittles, Elisa Pignatti, Giuliana Montosi, Cinzia Garuti, Innocent T. Gangaidzo, Z. A R Gomo, Victor M. Moyo, Tracey A. Rouault, Patrick MacPhail, Antonello Pietrangelo

Research output: Contribution to journalArticle

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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 μg/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 μg/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.

Original languageEnglish (US)
Pages (from-to)299-304
Number of pages6
JournalBlood Cells, Molecules, and Diseases
Volume31
Issue number3
DOIs
StatePublished - Nov 2003
Externally publishedYes

Fingerprint

African Americans
Ferritins
Mutation
Iron Overload
Iron
Genes
Serum
Anemia
Hemoglobins
Southern Africa
Transferrin
Heterozygote
Transferases
Aspartic Acid
Population
Bantu siderosis
metal transporting protein 1
Macrophages
Alcohols
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Hematology

Cite this

Gordeuk, V. R., Caleffi, A., Corradini, E., Ferrara, F., Jones, R. A., Castro, O., ... Pietrangelo, A. (2003). Iron overload in Africans and African-Americans and a common mutation in the SCL40A1 (ferroportin 1) gene. Blood Cells, Molecules, and Diseases, 31(3), 299-304. https://doi.org/10.1016/S1079-9796(03)00164-5

Iron overload in Africans and African-Americans and a common mutation in the SCL40A1 (ferroportin 1) gene. / Gordeuk, Victor R.; Caleffi, Angela; Corradini, Elena; Ferrara, Francesca; Jones, Russell A.; Castro, Oswaldo; Onyekwere, Onyinye; Kittles, Rick A; Pignatti, Elisa; Montosi, Giuliana; Garuti, Cinzia; Gangaidzo, Innocent T.; Gomo, Z. A R; Moyo, Victor M.; Rouault, Tracey A.; MacPhail, Patrick; Pietrangelo, Antonello.

In: Blood Cells, Molecules, and Diseases, Vol. 31, No. 3, 11.2003, p. 299-304.

Research output: Contribution to journalArticle

Gordeuk, VR, Caleffi, A, Corradini, E, Ferrara, F, Jones, RA, Castro, O, Onyekwere, O, Kittles, RA, Pignatti, E, Montosi, G, Garuti, C, Gangaidzo, IT, Gomo, ZAR, Moyo, VM, Rouault, TA, MacPhail, P & Pietrangelo, A 2003, 'Iron overload in Africans and African-Americans and a common mutation in the SCL40A1 (ferroportin 1) gene', Blood Cells, Molecules, and Diseases, vol. 31, no. 3, pp. 299-304. https://doi.org/10.1016/S1079-9796(03)00164-5
Gordeuk, Victor R. ; Caleffi, Angela ; Corradini, Elena ; Ferrara, Francesca ; Jones, Russell A. ; Castro, Oswaldo ; Onyekwere, Onyinye ; Kittles, Rick A ; Pignatti, Elisa ; Montosi, Giuliana ; Garuti, Cinzia ; Gangaidzo, Innocent T. ; Gomo, Z. A R ; Moyo, Victor M. ; Rouault, Tracey A. ; MacPhail, Patrick ; Pietrangelo, Antonello. / Iron overload in Africans and African-Americans and a common mutation in the SCL40A1 (ferroportin 1) gene. In: Blood Cells, Molecules, and Diseases. 2003 ; Vol. 31, No. 3. pp. 299-304.
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AU - Gordeuk, Victor R.

AU - Caleffi, Angela

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AU - Ferrara, Francesca

AU - Jones, Russell A.

AU - Castro, Oswaldo

AU - Onyekwere, Onyinye

AU - Kittles, Rick A

AU - Pignatti, Elisa

AU - Montosi, Giuliana

AU - Garuti, Cinzia

AU - Gangaidzo, Innocent T.

AU - Gomo, Z. A R

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