SORA

Advancing, promoting and sharing knowledge of health through excellence in teaching, clinical practice and research into the prevention and treatment of illness

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; et al. 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. e15085. ISSN 2050-084X https://doi.org/10.7554/eLife.15085
SGUL Authors: Molloy, Sile

[img]
Preview
PDF Published Version
Available under License Creative Commons Attribution.

Download (3MB) | Preview

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
Additional Information: © 2017, Clarke et al. This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited.
Keywords: G6PD deficiency, epidemiology, evolutionary biology, genetic association, genomics, global health, human, infectious disease, selection, Alleles, Anemia, Case-Control Studies, Glucosephosphate Dehydrogenase, Glucosephosphate Dehydrogenase Deficiency, Humans, Malaria, Cerebral, Malaria, Falciparum, Risk Assessment
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Elife
ISSN: 2050-084X
Language: eng
Dates:
DateEvent
9 January 2017Published
3 November 2016Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
G0600230Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MR/M006212/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
G19/9Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
G0600718Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MC_UP_A900_1118Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
090770/Z/09/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
566Foundation for the National Institutes of Healthhttp://dx.doi.org/10.13039/100000009
097364/Z/11/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
LSHP-CT-2004-503578European Commissionhttp://dx.doi.org/10.13039/501100000780
077383/Z/05/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
087285Wellcome Trusthttp://dx.doi.org/10.13039/100004440
096527Wellcome Trusthttp://dx.doi.org/10.13039/100004440
090532/Z/09/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
077012/Z/05/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
LSHP-CT-2004–503578BioMalPar European Network of ExcellenceUNSPECIFIED
076934/Z/05/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
091758/Z/10/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
242095Seventh Framework Programmehttp://dx.doi.org/10.13039/501100004963
084538Wellcome Trusthttp://dx.doi.org/10.13039/100004440
G9901439Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
SANTE/2004/078–607European Commissionhttp://dx.doi.org/10.13039/501100000780
089276/Z/09/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
PubMed ID: 28067620
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/110058
Publisher's version: https://doi.org/10.7554/eLife.15085

Actions (login required)

Edit Item Edit Item