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Variation in the ICAM1 gene is not associated with severe malaria phenotypes

Genes & Immunity volume 9, pages 462–469 (2008)Cite this article

Abstract

Evidence from autopsy and in vitro binding studies suggests that adhesion of erythrocytes infected with Plasmodium falciparum to the human host intercellular adhesion molecule (ICAM)-1 receptor is important in the pathogenesis of severe malaria. Previous association studies between polymorphisms in the ICAM1 gene and susceptibility to severe malarial phenotypes have been inconclusive and often contradictory. We performed genetic association studies with 15 single nucleotide polymorphisms (SNPs) around the ICAM1 locus. All SNPs were screened in a family study of 1071 trios from The Gambia, Malawi and Kenya. Two key non-synonymous SNPs with previously reported associations, rs5491 (K56M or ‘ICAM-1Kilifi’) and rs5498 (K469E), were tested in an additional 708 Gambian trios and a case-control study of 4058 individuals. None of the polymorphisms were associated with severe malaria phenotypes. Pooled results across our studies for ICAM-1Kilifi were, in severe malaria, odds ratio (OR) 1.02, 95% confidence interval (CI) 0.96–1.09, P=0.54, and cerebral malaria OR 1.07, CI 0.97–1.17, P=0.17. We assess the available epidemiological, population genetic and functional evidence that links ICAM-1Kilifi to severe malaria susceptibility.

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Acknowledgements

This work was funded by a Wellcome Trust Clinical Research Training Fellowship (to AEF) and the UK Medical Research Council (to DPK). This manuscript is published with the permission of the director of the Kenya Medical Research Institute. TW was funded by the Wellcome Trust, MalariaGEN and the European Union Network 6 BioMalPar Consortium.

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Author notes

  1. J Wilson: Deceased.

Authors and Affiliations

  1. The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford, UK

    A E Fry, S Auburn, M Diakite, A Green, A Richardson, J Wilson, M J Griffiths, K A Rockett & D P Kwiatkowski

  2. Medical Research Council, Banjul, The Gambia

    M Jallow, F Sisay-Joof & M Pinder

  3. Kenya Medical Research Institute Centre for Geographical Medicine Research (Coast), Kilifi, Kenya

    M J Griffiths, N Peshu, T N Williams & K Marsh

  4. Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, UK

    T N Williams & K Marsh

  5. Malawi–Liverpool–Wellcome Trust Programme of Clinical Tropical Research, Blantyre, Malawi

    M E Molyneux

  6. Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, UK

    M E Molyneux

  7. Blantyre Malaria Project, College of Medicine, Blantyre, Malawi

    T E Taylor

  8. Department of Internal Medicine, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA

    T E Taylor

  9. Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

    D P Kwiatkowski

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  1. A E Fry
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Correspondence to A E Fry.

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Fry, A., Auburn, S., Diakite, M. et al. Variation in the ICAM1 gene is not associated with severe malaria phenotypes. Genes Immun 9, 462–469 (2008). https://doi.org/10.1038/gene.2008.38

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