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DOI 10.7554/elife.15085

Медицинская библиотека · eLife · 2017

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

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, Thera Mahamadou A, Konate Salimata, Sissoko Sibiry, Niangaly Amadou, Poudiougou Belco, Mangano Valentina D, 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 Ca, Agbenyega Tsiri, Achidi Eric, Doumbo Ogobara K, Farrar Jeremy, Marsh Kevin, Taylor Terrie, Kwiatkowski Dominic P, MalariaGEN Consortium

СтатьяМногоцентровое исследованиеПоддержка исследования: вне правительства СШАПеревод в очереди

Аннотация

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.

Для цитирования: 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, Thera Mahamadou A, Konate Salimata, Sissoko Sibiry, Niangaly Amadou, Poudiougou Belco, Mangano Valentina D, 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 Ca, Agbenyega Tsiri, Achidi Eric, Doumbo Ogobara K, Farrar Jeremy, Marsh Kevin, Taylor Terrie, Kwiatkowski Dominic P, MalariaGEN Consortium. Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia.. eLife. 2017. DOI: 10.7554/elife.15085.

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