Journal
ELIFE
Volume 6, Issue -, Pages -Publisher
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLIFE.15085
Keywords
-
Categories
Funding
- Wellcome Trust [090770/Z/09/Z, 097364/Z/11/Z, 076934/Z/05/Z, 091758/Z/10/Z, 084538, 089276/Z/09/Z, 077383/Z/05/Z, 090532/Z/09/Z, 077012/Z/05/Z, 087285, 096527]
- Foundation for the National Institutes of Health [566]
- European Commission [LSHP-CT-2004-503578, SANTE/2004/078-607]
- National Institute of Allergy and Infectious Diseases
- European and Developing Countries Clinical Trials Partnership
- National Health and Medical Research Council
- Fogarty International Center
- Seventh Framework Programme [242095]
- Royal Australasian College of Physicians
- Medical Research Council [G9901439, G0600718, G0600230, G19/9]
- MRC [G0600230, MC_UP_A900_1118, MR/M006212/1, G19/9, G0600718] Funding Source: UKRI
- Medical Research Council [MC_UP_A900_1118, G0600718, MR/M006212/1, G0600230, G19/9] Funding Source: researchfish
- Wellcome Trust [204911/Z/16/Z] Funding Source: researchfish
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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 individuals 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.
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