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CD40L association with protection from severe malaria

Genes & Immunity volume 3, pages 286–291 (2002)Cite this article

Abstract

CD40 ligand (CD40L), a glycoprotein involved in B cell proliferation, antigen presenting cell activation, and Ig class switching, is important in the immune response to infection. Rare coding mutations in CD40L can lead to life-threatening immunodeficiency but the potential for common variants to alter disease susceptibility remains to be explored. To identify polymorphisms in CD40L, we sequenced 2.3 kb of the 5′ flanking region and the first exon of the gene in DNA samples from 36 Gambian females and one chimpanzee. Diversity was lower than the average reported for other areas of the X chromosome, and only two polymorphisms were identified. The polymorphisms were genotyped in DNA samples from 957 Gambian individuals, cases and controls from a study of severe malaria. A significant reduction in risk for severe malaria (OR = 0.52, P = 0.002) was associated with males hemizygous for the CD40L−726C. Analysis by transmission disequilibrium test of 371 cases, for whom DNA from both parents was also available, confirmed the result was not due to stratification (P = 0.04). A similar but non-significant trend was found in females. This preliminary association of a common variant in CD40L with a malaria resistance phenotype encourages further genetic characterization of the role of CD40L in infectious disease.

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Acknowledgements

We thank David Reich, Shiv Pillai and Joel Hirschorn for many thoughtful discussions and comments and Nick Mundy for the chimpanzee DNA sample. This study would not have been possible without the kind cooperation of the families studied, and the doctors and nurses of RVH, Banjul, The Gambia.

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Authors and Affiliations

  1. Wellcome Trust Centre for Human Genetics, Oxford, UK

    P Sabeti, S Farhadian & D Kwiatkowski

  2. MRC Laboratories, Fajara, The Gambia

    S Usen, M Jallow, T Doherty, M Newport & M Pinder

  3. Institute of Biological Anthropology, Oxford University, Oxford, UK

    P Sabeti & R Ward

  4. Royal Victoria Hospital, Banjul, The Gambia

    M Jallow

Authors
  1. P Sabeti
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  2. S Usen
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  3. S Farhadian
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  4. M Jallow
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  5. T Doherty
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  6. M Newport
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  7. M Pinder
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  8. R Ward
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  9. D Kwiatkowski
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Corresponding author

Correspondence to D Kwiatkowski.

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This study was funded by the Medical Research Council and the Rhodes Scholarship Trust.

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Sabeti, P., Usen, S., Farhadian, S. et al. CD40L association with protection from severe malaria. Genes Immun 3, 286–291 (2002). https://doi.org/10.1038/sj.gene.6363877

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  • DOI: https://doi.org/10.1038/sj.gene.6363877

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