The ferroportin Q248H mutation protects from anemia, but not malaria or bacteremia
| Autor: | Deepti Gurdasani, James J. Gilchrist, Emily L. Webb, Sodiomon B. Sirima, Thomas N. Williams, Cristina Pomilla, J. Anthony G. Scott, Alison M. Elliott, Dominic P. Kwiatkowski, Anna Rautanen, Swaib A. Lule, Wandia Kimita, Fatou Joof, Reagan M. Mogire, Francis M. Ndungu, Alexander J. Mentzer, Amidou Diarra, Shabir A. Madhi, Philip Bejon, Neema Mturi, Sarah H. Atkinson, Tommy Carstensen, Morgan M. Goheen, Carla Cerami, Adrian V. S. Hill, Alireza Morovat, Kirk A. Rockett, Manjinder S. Sandhu, Andrew M. Prentice, Clare L. Cutland, John Muthii Muriuki, Gavin Band |
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| Přispěvatelé: | Muriuki, John Muthii [0000-0003-4369-9547], Mentzer, Alexander J [0000-0002-4502-2209], Band, Gavin [0000-0002-1710-9024], Gilchrist, James J [0000-0003-2045-6788], Carstensen, Tommy [0000-0002-3672-9931], Goheen, Morgan M [0000-0003-2297-3295], Kimita, Wandia [0000-0002-3099-7134], Mogire, Reagan [0000-0001-6454-1613], Cutland, Clare L [0000-0001-8250-8307], Pomilla, Cristina [0000-0002-2581-8365], Gurdasani, Deepti [0000-0001-9996-6929], Rockett, Kirk [0000-0002-6369-9299], Mturi, Neema [0000-0002-6585-2074], Ndungu, Francis M [0000-0002-8977-0030], Sirima, Sodiomon B [0000-0002-0972-4211], Morovat, Alireza [0000-0002-5832-7992], Prentice, Andrew M [0000-0001-5389-451X], Webb, Emily L [0000-0002-4019-7456], Elliott, Alison M [0000-0003-2818-9549], Hill, Adrian VS [0000-0003-0900-9629], Kwiatkowski, Dominic P [0000-0002-5023-0176], Cerami, Carla [0000-0002-7634-0955], Atkinson, Sarah H [0000-0002-8360-4402], Apollo - University of Cambridge Repository, Wellcome Trust |
| Rok vydání: | 2019 |
| Předmět: |
Hemolytic anemia
Male Erythrocytes Anemia Iron Ferroportin Mutation Missense Bacteremia medicine.disease_cause 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases parasitic diseases Medicine Humans Health and Medicine Cation Transport Proteins Research Articles 030304 developmental biology 0303 health sciences Mutation Multidisciplinary biology business.industry Infant Newborn SciAdv r-articles Infant Iron deficiency Iron Deficiencies medicine.disease Hemolysis 3. Good health Malaria Glutamine Amino Acid Substitution 030220 oncology & carcinogenesis Immunology biology.protein Female business Research Article |
| Zdroj: | Science Advances |
| ISSN: | 2375-2548 |
| Popis: | The FPN Q248H mutation protects children from anemia, hemolysis, and iron deficiency, but not malaria or bacterial infection. 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. |
| Databáze: | OpenAIRE |
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