African glucose-6-phosphate dehydrogenase alleles associated with protection from severe malaria in heterozygous females in Tanzania.
X-linked Glucose-6-phosphate dehydrogenase (G6PD) A- deficiency is prevalent in sub-Saharan Africa populations, and has been associated with protection from severe malaria. Whether females and/or males are protected by G6PD deficiency is uncertain, due in part to G6PD and malaria phenotypic complexi...
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Public Library of Science (PLoS)
2015-02-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1004960&type=printable |
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| author | Alphaxard Manjurano Nuno Sepulveda Behzad Nadjm George Mtove Hannah Wangai Caroline Maxwell Raimos Olomi Hugh Reyburn Eleanor M Riley Christopher J Drakeley Taane G Clark MalariaGEN Consortium |
| author_facet | Alphaxard Manjurano Nuno Sepulveda Behzad Nadjm George Mtove Hannah Wangai Caroline Maxwell Raimos Olomi Hugh Reyburn Eleanor M Riley Christopher J Drakeley Taane G Clark MalariaGEN Consortium |
| author_sort | Alphaxard Manjurano |
| collection | DOAJ |
| description | X-linked Glucose-6-phosphate dehydrogenase (G6PD) A- deficiency is prevalent in sub-Saharan Africa populations, and has been associated with protection from severe malaria. Whether females and/or males are protected by G6PD deficiency is uncertain, due in part to G6PD and malaria phenotypic complexity and misclassification. Almost all large association studies have genotyped a limited number of G6PD SNPs (e.g. G6PD202 / G6PD376), and this approach has been too blunt to capture the complete epidemiological picture. Here we have identified 68 G6PD polymorphisms and analysed 29 of these (i.e. those with a minor allele frequency greater than 1%) in 983 severe malaria cases and controls in Tanzania. We establish, across a number of SNPs including G6PD376, that only female heterozygotes are protected from severe malaria. Haplotype analysis reveals the G6PD locus to be under balancing selection, suggesting a mechanism of protection relying on alleles at modest frequency and avoiding fixation, where protection provided by G6PD deficiency against severe malaria is offset by increased risk of life-threatening complications. Our study also demonstrates that the much-needed large-scale studies of severe malaria and G6PD enzymatic function across African populations require the identification and analysis of the full repertoire of G6PD genetic markers. |
| format | Article |
| id | doaj-art-e9353f36c7a5467982dfadb0b1bd646c |
| institution | Kabale University |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2015-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-e9353f36c7a5467982dfadb0b1bd646c2025-08-20T03:46:13ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042015-02-01112e100496010.1371/journal.pgen.1004960African glucose-6-phosphate dehydrogenase alleles associated with protection from severe malaria in heterozygous females in Tanzania.Alphaxard ManjuranoNuno SepulvedaBehzad NadjmGeorge MtoveHannah WangaiCaroline MaxwellRaimos OlomiHugh ReyburnEleanor M RileyChristopher J DrakeleyTaane G ClarkMalariaGEN ConsortiumX-linked Glucose-6-phosphate dehydrogenase (G6PD) A- deficiency is prevalent in sub-Saharan Africa populations, and has been associated with protection from severe malaria. Whether females and/or males are protected by G6PD deficiency is uncertain, due in part to G6PD and malaria phenotypic complexity and misclassification. Almost all large association studies have genotyped a limited number of G6PD SNPs (e.g. G6PD202 / G6PD376), and this approach has been too blunt to capture the complete epidemiological picture. Here we have identified 68 G6PD polymorphisms and analysed 29 of these (i.e. those with a minor allele frequency greater than 1%) in 983 severe malaria cases and controls in Tanzania. We establish, across a number of SNPs including G6PD376, that only female heterozygotes are protected from severe malaria. Haplotype analysis reveals the G6PD locus to be under balancing selection, suggesting a mechanism of protection relying on alleles at modest frequency and avoiding fixation, where protection provided by G6PD deficiency against severe malaria is offset by increased risk of life-threatening complications. Our study also demonstrates that the much-needed large-scale studies of severe malaria and G6PD enzymatic function across African populations require the identification and analysis of the full repertoire of G6PD genetic markers.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1004960&type=printable |
| spellingShingle | Alphaxard Manjurano Nuno Sepulveda Behzad Nadjm George Mtove Hannah Wangai Caroline Maxwell Raimos Olomi Hugh Reyburn Eleanor M Riley Christopher J Drakeley Taane G Clark MalariaGEN Consortium African glucose-6-phosphate dehydrogenase alleles associated with protection from severe malaria in heterozygous females in Tanzania. PLoS Genetics |
| title | African glucose-6-phosphate dehydrogenase alleles associated with protection from severe malaria in heterozygous females in Tanzania. |
| title_full | African glucose-6-phosphate dehydrogenase alleles associated with protection from severe malaria in heterozygous females in Tanzania. |
| title_fullStr | African glucose-6-phosphate dehydrogenase alleles associated with protection from severe malaria in heterozygous females in Tanzania. |
| title_full_unstemmed | African glucose-6-phosphate dehydrogenase alleles associated with protection from severe malaria in heterozygous females in Tanzania. |
| title_short | African glucose-6-phosphate dehydrogenase alleles associated with protection from severe malaria in heterozygous females in Tanzania. |
| title_sort | african glucose 6 phosphate dehydrogenase alleles associated with protection from severe malaria in heterozygous females in tanzania |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1004960&type=printable |
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