ArticlePLoS genetics2015
African glucose-6-phosphate dehydrogenase alleles associated with protection from severe malaria in heterozygous females in Tanzania.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 89 citations in OpenAlex.
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- Circulating Immune Complexes and Glucose-6-Phosphate Dehydrogenase Deficiency Predict Recurrent Blackwater Fever in Ugandan Children With Severe Malaria.The Journal of infectious diseases · 2025Article
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- Prevalence of G6PD deficiency and submicroscopic malaria parasites carriage in malaria hotspot area in Northwest, Tanzania.Malaria journal · 2023Article
- High throughput human genotyping for variants associated with malarial disease outcomes using custom targeted amplicon sequencing.Scientific reports · 2023Article
- Hemoglobinopathies, merozoite surface protein-2 gene polymorphisms, and acquisition of Epstein Barr virus among infants in Western Kenya.BMC cancer · 2023Article
- Biology and epidemiology ofParasite epidemiology and control · 2023Review
- Functional interpretation, cataloging, and analysis of 1,341 glucose-6-phosphate dehydrogenase variants.American journal of human genetics · 2023Article
- Duffy blood system and G6PD genetic variants in vivax malaria patients from Manaus, Amazonas, Brazil.Malaria journal · 2022Article
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- G6PD distribution in sub-Saharan Africa and potential risks of using chloroquine/hydroxychloroquine based treatments for COVID-19.The pharmacogenomics journal · 2021Article
- Protecting future antimalarials from the trap of resistance: Lessons from artemisinin-based combination therapy (ACT) failures.Journal of pharmaceutical analysis · 2021Review
- G6PD Polymorphisms and Hemolysis After Antimalarial Treatment With Low Single-Dose Primaquine: A Pooled Analysis of Six African Clinical Trials.Frontiers in genetics · 2021Article
- Knowlesi malaria: Human risk factors, clinical spectrum, and pathophysiology.Advances in parasitology · 2021Article
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- Traditional African remedies induce hemolysis in a glucose-6-phopshate dehydrogenase deficient zebrafish model.Scientific reports · 2020Article
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- Platelet and hemoglobin count at diagnosis are associated with survival in African American and Caucasian patients with colorectal cancer.Cancer epidemiology · 2020Article
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
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.
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