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

MalariaGEN Consortium, Geraldine M Clarke, Kirk A Rockett, Katja Kivinen, Christina Hubbart, Anna E Jeffreys, Kate Rowlands, Muminatou Jallow, David J. Conway, Kalifa A Bojang, Margaret Pinder, Stanley Usen, Fatoumatta Sisay-Joof, Giorgio Sirugo, Ousmane Toure, Mahamadou A. Thera, Salimata Konate, Sibiry Sissoko, Amadou Niangaly, Belco PoudiougouValentina D Mangano, Edith C Bougouma, Sodiomon B Sirima, David Modiano, Lucas N Amenga-Etego, Anita Ghansah, Kwadwo A Koram, Michael D Wilson, Anthony Enimil, Jennifer Evans, Olukemi K Amodu, Subulade Olaniyan, Tobias Apinjoh, Regina Mugri, Andre Ndi, Carolyne M Ndila, Sophie Uyoga, Alexander Macharia, Norbert Peshu, Thomas N Williams, Alphaxard Manjurano, Nuno Sepúlveda, Taane G Clark, Eleanor Riley, Chris Drakeley, Hugh Reyburn, Vysaul Nyirongo, David Kachala, Malcolm E. Molyneux, Sarah J. Dunstan, Nguyen Hoan Phu

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection againstPlasmodium falciparummalaria, 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 ofP. falciparuminfection. 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 ofP. falciparuminfection could have been a major cause of the high levels of G6PD polymorphism seen in human populations.

Original languageEnglish
JournaleLIFE
Volume6
DOIs
Publication statusPublished - 9 Jan 2017

Keywords / Materials (for Non-textual outputs)

  • Alleles
  • Anemia
  • Case-Control Studies
  • Glucosephosphate Dehydrogenase
  • Glucosephosphate Dehydrogenase Deficiency
  • Humans
  • Malaria, Cerebral
  • Malaria, Falciparum
  • Risk Assessment
  • Journal Article
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

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