Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia
| Title: | Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia |
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| Authors: | 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; A. Thera, Mahamadou; Konate, Salimata; Sissoko, Sibiry; Niangaly, Amadou; Poudiougou, Belco; MANGANO, VALENTINA; 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; 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 C. A.; Agbenyega, Tsiri; Achidi, Eric; Doumbo, Ogobara K.; Farrar, Jeremy; Marsh, Kevin; Taylor, Terrie; Kwiatkowski, Dominic P.; Consortium, Malariagen |
| Contributors: | 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; A. Thera, Mahamadou; Konate, Salimata; Sissoko, Sibiry; Niangaly, Amadou; Poudiougou, Belco; Mangano, Valentina; 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, Tobia; 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, Chri; Reyburn, Hugh; Nyirongo, Vysaul; Kachala, David; Molyneux, Malcolm; Dunstan, Sarah J.; Phu, Nguyen Hoan; Quyen, Nguyen Ngoc; Thai, Cao Quang; Hien, Tran Tinh; Manning, Lauren; Laman, Mose; 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 C. A.; Agbenyega, Tsiri; Achidi, Eric; Doumbo, Ogobara K.; Farrar, Jeremy; Marsh, Kevin; Taylor, Terrie; Kwiatkowski, Dominic P.; Consortium, Malariagen |
| Publisher Information: | eLife Sciences Publications Ltd |
| Publication Year: | 2017 |
| Collection: | Sapienza Università di Roma: CINECA IRIS |
| Subject Terms: | g6pd deficiency; epidemiology; evolutionary biology; genetic association; genomic; global health; human; infectious disease; selection; neuroscience (all); medicine (all); immunology and microbiology (all); biochemistry; genetics and molecular biology (all) |
| Description: | 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 multicentre 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. |
| Document Type: | article in journal/newspaper |
| File Description: | STAMPA |
| Language: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/28067620; info:eu-repo/semantics/altIdentifier/wos/WOS:000393387700001; volume:6; firstpage:1; lastpage:30; numberofpages:30; journal:ELIFE; http://hdl.handle.net/11573/956410 |
| DOI: | 10.7554/eLife.15085 |
| Availability: | http://hdl.handle.net/11573/956410; https://doi.org/10.7554/eLife.15085; https://elifesciences.org/content/6/e15085-download.pdf |
| Rights: | info:eu-repo/semantics/openAccess |
| Accession Number: | edsbas.4B9C3CF6 |
| Database: | BASE |