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Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia.

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Clarke, Geraldine M, Rockett, Kirk, Kivinen, Katja, Hubbart, Christina, Jeffreys, Anna E, Rowlands, Kate, Jallow, Muminatou, Conway, David J, Bojang, Kalifa A, Pinder, Margaret, Usen, Stanley, Sisay-Joof, Fatoumatta, Sirugo, Giorgio, Toure, Ousmane, Thera, Mahamadou A, Konate, Salimata, Sissoko, Sibiry, Niangaly, Amadou, Poudiougou, Belco, Mangano, Valentina D, Bougouma, Edith C, Sirima, Sodiomon B, Modiano, David, Amenga-Etego, Lucas N, Ghansah, Anita, Koram, Kwadwo A, Wilson, Michael D, Enimil, Anthony, Evans, Jennifer, Amodu, Olukemi K, Olaniyan, Subulade, Apinjoh, Tobias, Mugri, Regina, Ndi, Andre, Ndila, Carolyne M, Uyoga, Sophie, Macharia, Alexander, Peshu, Norbert, Williams, Thomas N, Manjurano, Alphaxard, Sepúlveda, Nuno, Clark, Taane G, Riley, Eleanor, Drakeley, Chris, Reyburn, Hugh, Nyirongo, Vysaul, Kachala, David, Molyneux, Malcolm E, Dunstan, Sarah J, Phu, Nguyen Hoan, Quyen, Nguyen Ngoc, Thai, Cao Quang, Hien, Tran Tinh, Manning, Laurens, Laman, Moses, Siba, Peter, Karunajeewa, Harin, Allen, Steve, Allen, Angela, Davis, Timothy Me, Michon, Pascal, Mueller, Ivo, Molloy, Síle F, Campino, Susana, Kerasidou, Angeliki, Cornelius, Victoria J, Hart, Lee, Shah, Shivang S, Band, Gavin, Spencer, Chris Ca, Agbenyega, Tsiri, Achidi, Eric, Doumbo, Ogobara K, Farrar, Jeremy, Marsh, Kevin, Taylor, Terrie and Kwiatkowski, Dominic P (2017) 'Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia.'. eLife, Vol 6, e15085.

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Abstract

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effect has proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual’s level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia. Models of balancing selection based on these findings indicate that an evolutionary trade-off between different clinical outcomes of P. falciparum infection could have been a major cause of the high levels of G6PD polymorphism seen in human populations.

Item Type: Article
Subjects: QU Biochemistry > Enzymes > QU 135 Enzymes
QU Biochemistry > Genetics > QU 460 Genomics. Proteomics
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 755 Epidemiology
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.7554/elife.15085
SWORD Depositor: JISC Pubrouter
Depositing User: JISC Pubrouter
Date Deposited: 23 Feb 2017 13:53
Last Modified: 17 Jul 2020 10:58
URI: https://archive.lstmed.ac.uk/id/eprint/6843

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