The ferroportin Q248H mutation protects from anemia, but not malaria or bacteremia.

Muriuki, JMORCID logo; Mentzer, AJORCID logo; Band, GORCID logo; Gilchrist, JJORCID logo; Carstensen, TORCID logo; Lule, SA; Goheen, MMORCID logo; Joof, F; Kimita, WORCID logo; Mogire, RORCID logo; +22 more...Cutland, CLORCID logo; Diarra, A; Rautanen, A; Pomilla, CORCID logo; Gurdasani, DORCID logo; Rockett, KORCID logo; Mturi, NORCID logo; Ndungu, FMORCID logo; Scott, JAGORCID logo; Sirima, SBORCID logo; Morovat, AORCID logo; Prentice, AMORCID logo; Madhi, SA; Webb, ELORCID logo; Elliott, AMORCID logo; Bejon, P; Sandhu, MS; Hill, AVORCID logo; Kwiatkowski, DPORCID logo; Williams, TN; Cerami, CORCID logo; Atkinson, SHORCID logo and (2019) The ferroportin Q248H mutation protects from anemia, but not malaria or bacteremia. Science Advances, 5 (9). eaaw0109-. ISSN 2375-2548 DOI: 10.1126/sciadv.aaw0109
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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.


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