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


Clarke, GM; Rockett, K; Kivinen, K; Hubbart, C; Jeffreys, AE; Rowlands, K; Jallow, M; Conway, DJ; Bojang, KA; Pinder, M; Usen, S; Sisay-Joof, F; Sirugo, G; Toure, O; Thera, MA; Konate, S; Sissoko, S; Niangaly, A; Poudiougou, B; Mangano, VD; Bougouma, EC; Sirima, SB; Modiano, D; Amenga-Etego, LN; Ghansah, A; Koram, KA; Wilson, MD; Enimil, A; Evans, J; Amodu, OK; Olaniyan, S; Apinjoh, T; Mugri, R; Ndi, A; Ndila, CM; Uyoga, S; Macharia, A; Peshu, N; Williams, TN; Manjurano, A; Sepúlveda, N; Clark, TG; Riley, E; Drakeley, C; Reyburn, H; Nyirongo, V; Kachala, D; Molyneux, M; Dunstan, SJ; Phu, NH; Quyen, NN; Thai, CQ; Hien, TT; Manning, L; Laman, M; Siba, P; Karunajeewa, H; Allen, S; Allen, A; Davis, TM; Michon, P; Mueller, I; Molloy, SF; Campino, S; Kerasidou, A; Cornelius, VJ; Hart, L; Shah, SS; Band, G; Spencer, CC; Agbenyega, T; Achidi, E; Doumbo, OK; Farrar, J; Marsh, K; Taylor, T; Kwiatkowski, DP; MalariaGEN Consortium, ; (2017) Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia. Elife, 6. ISSN 2050-084X DOI: 10.7554/eLife.15085

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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 effecthas 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
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Research Centre: Malaria Centre
PubMed ID: 28067620
Web of Science ID: 393387700001
URI: http://researchonline.lshtm.ac.uk/id/eprint/3356622

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