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Creating deaths from malaria

Nature Genetics volume 22, pages 120–121 (1999)Cite this article

The effect of malaria is diffracted by a myriad of genetic modifications that appear in affected areas. The best-known example is sickle-cell disease, in which individuals heterozygous for mutated haemoglobin alleles have a survival advantage when infected with malaria, relative to homozygous mutant or wild-type individuals. The α- and β-thalassaemias and glucose-6-phosphate dehydrogenase deficiency are other examples of mutations in human genes which, in a heterozygous condition, can protect against malaria. Of the cytokines, tumour-necrosis factor (TNF), in particular, has been implicated in the pathogenesis of severe malaria2. On page 145 of this issue, Knight et al.3 present a study that uncovers how 3 polymorphisms in the promoter region of TNF contribute to malarial pathogenesis. One such polymorphism, TNF–376A, augments the secretion of TNF by recruiting the transcription factor OCT-1 (ref. 3).

Support for the role of TNF in the pathogenesis of malaria lies in the finding that a polymorphism in the promoter region of TNF governs the outcome of the disease. People who carry the TNF2 allele with this polymorphism are more prone to severe malaria6—in contrast to the protection afforded by the mutation that causes sickle-cell disease. The disadvantage conferred by the polymorphism must be counterbalanced by a weighty advantage for it to remain frequent in the population.

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Figure 1: A malaria world.
Figure 2: Mechanisms proposed to be involved in the pathogenesis of severe malaria.

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  1. Microbiology and Tumour Biology Centre, Karolinska Institutet, and Swedish Institute for Infectious Disease Control, Stockholm, S-171 77, Sweden

    Mats Wahlgren

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  1. Mats Wahlgren
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Wahlgren, M. Creating deaths from malaria. Nat Genet 22, 120–121 (1999). https://doi.org/10.1038/9621

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