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.