The ferroportin Q248H mutation protects from anemia, but not malaria or bacteremia.
Published version
Peer-reviewed
Repository URI
Repository DOI
Change log
Authors
Abstract
Iron acquisition is critical for life. Ferroportin (FPN) exports iron from mature erythrocytes, and deletion of the Fpn gene results in hemolytic anemia and increased fatality in malaria-infected mice. The FPN Q248H mutation (glutamine to histidine at position 248) renders FPN partially resistant to hepcidin-induced degradation and was associated with protection from malaria in human studies of limited size. Using data from cohorts including over 18,000 African children, we show that the Q248H mutation is associated with modest protection against anemia, hemolysis, and iron deficiency, but we found little evidence of protection against severe malaria or bacteremia. We additionally observed no excess Plasmodium growth in Q248H erythrocytes ex vivo, nor evidence of selection driven by malaria exposure, suggesting that the Q248H mutation does not protect from malaria and is unlikely to deprive malaria parasites of iron essential for their growth.
Description
Keywords
Journal Title
Conference Name
Journal ISSN
2375-2548
Volume Title
Publisher
Publisher DOI
Sponsorship
Medical Research Council (MR/K013491/1)
Wellcome Trust (090770/Z/09/Z)
Wellcome Trust (107743/Z/15/Z)
Medical Research Council (G0901213/1)