title: Iron overload in Africans and African-Americans and a common mutation in the SCL40A1 (ferroportin 1) gene.
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.
authors.affiliation: Howard University College of Medicine, Washington, DC 20059, USA.
authors.forename: Victor R
authors.initials: VR
authors.lastname: Gordeuk
authors.forename: Angela
authors.initials: A
authors.lastname: Caleffi
authors.forename: Elena
authors.initials: E
authors.lastname: Corradini
authors.forename: Francesca
authors.initials: F
authors.lastname: Ferrara
authors.forename: Russell A
authors.initials: RA
authors.lastname: Jones
authors.forename: Oswaldo
authors.initials: O
authors.lastname: Castro
authors.forename: Onyinye
authors.initials: O
authors.lastname: Onyekwere
authors.forename: Rick
authors.initials: R
authors.lastname: Kittles
authors.forename: Elisa
authors.initials: E
authors.lastname: Pignatti
authors.forename: Giuliana
authors.initials: G
authors.lastname: Montosi
authors.forename: Cinzia
authors.initials: C
authors.lastname: Garuti
authors.forename: Innocent T
authors.initials: IT
authors.lastname: Gangaidzo
authors.forename: Z A R
authors.initials: ZA
authors.lastname: Gomo
authors.forename: Victor M
authors.initials: VM
authors.lastname: Moyo
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Rouault
authors.forename: Patrick
authors.initials: P
authors.lastname: MacPhail
authors.forename: Antonello
authors.initials: A
authors.lastname: Pietrangelo
mesh_terms: D001741:Black or African American / Q000235:genetics*; D001483:Base Sequence; D044383:Black People / Q000235:genetics*; D027682:Cation Transport Proteins / Q000235:genetics*; D005260:Female; D005293:Ferritins / Q000097:blood; D005973:Glutamine / Q000235:genetics / Q000378:metabolism; D006403:Hematologic Tests; D006639:Histidine / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000097:blood; D019190:Iron Overload / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D000098742:Ferroportin
chemical_list: D027682:Cation Transport Proteins; D000098742:Ferroportin; D005973:Glutamine; D006639:Histidine; D005293:Ferritins; D007501:Iron