Iron exporter mutations provide malaria protection but predispose African Americans to iron overload disease

2018

Challenge

Diseases caused by the body’s inability to properly process iron are common in Africa, in part due to a mutation in ferroportin, the protein that moves iron out of cells into the bloodstream. African Americans brought the mutation from Africa to the United States, where the mutation carrier rate of ferroportin is high at about eight percent. The mutation likely contributes to health disparities between African Americans and other U.S. populations, but its exact effects on red blood cells and the reason for its prevalence remained unclear.

Advance

IRP researchers, led by Tracey Rouault, M.D., discovered that this ferroportin mutation protects individuals from malaria infection, thereby explaining how it became common in Africa. However, the mutation also interferes with the body’s ability to regulate iron. This predisposes African Americans with the mutation to iron overload diseases, which are caused by an abnormal accumulation of iron in the body’s tissues.

Impact

This research has the potential to prevent the onset of diseases prevalent among African Americans by treating genetically identified patients and implementing therapies to reduce iron overload.

Publications

Zhang DL, Wu J, Shah BN, Greutélaers KC, Ghosh MC, Ollivierre H, Su XZ, Thuma PE, Bedu-Addo G, Mockenhaupt FP, Gordeuk VR, Rouault TA. (2018). Erythrocytic ferroportin reduces intracellular iron accumulation, hemolysis, and malaria risk. Science. Mar 30;359(6383):1520-1523.