Natural selection of hemi-and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria

C. Ruwende, S. C. Khoo, R. W. Snow, S. N R Yates, D. Kwlatkowskl, S. Gupta, P. Warn, C. E M Allsopp, S. C. Gilbert, N. Peschu, C. I. Newbold, B. M. Greenwood, K. Marsh, A. V S Hill

    Research output: Contribution to journalArticlepeer-review

    Abstract

    GLUCOSE-6-PHOSPHATE dehydrogenase (G6PD) deficiency, the most common enzymopathy of humans, affects over 400 million people1. The geographical correlation of its distribution with the historical endemicity of malaria suggests that this disorder has risen in frequency through natural selection by malaria2,3. However, attempts to confirm that G6PD deficiency is protective in case-control studies of malaria have yielded conflicting results4-8. Hence, for this X-linked disorder, it is unclear whether both male hemizygotes and female heterozygotes are protected or, as frequently suggested, only females1,5-11. Furthermore, how much protection may be afforded is unknown. Here we report that, in two large case-control studies of over 2,000 African children, the common African form of G6PD deficiency (G6PD A-) is associated with a 46-58% reduction in risk of severe malaria for both female heterozygotes and male hemizygotes. A mathematical model incorporating the measured selective advantage against malaria suggests that a counterbalancing selective disadvantage, associated with this enzyme deficiency, has retarded its rise in frequency in malaria-endemic regions. Although G6PD deficiency is now regarded as a generally benign disorder, in earlier environmental conditions it could have been significantly disadvantageous.
    Original languageEnglish
    Pages (from-to)246-XI
    JournalNature
    Volume376
    Issue number6537
    DOIs
    Publication statusPublished - 20 Jul 1995

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