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Interferon-alpha receptor-1 (IFNAR1) variants are associated with protection against cerebral malaria in The Gambia

Genes & Immunity volume 4, pages 275–282 (2003)Cite this article

Abstract

The chromosome 21q22.11 cytokine receptor cluster contains four genes that encode subunits of the receptors for the cytokines interleukin-10 and interferon-alpha, -beta and -gamma that may have a role in malaria pathogenesis. A total of 15 polymorphic markers located within these genes were initially genotyped in 190 controls and 190 severe malaria cases from The Gambia. Two interferon-alpha receptor-1 (IFNAR1) gene SNPs (17470 and L168 V) showed evidence for an association with severe malaria phenotypes and were typed in a larger series of samples comprising 538 severe malaria cases, 338 mild malaria cases and 562 controls. Both the 17470-G/G and L168V-G/G genotypes were associated with protection against severe malaria, in general, and cerebral malaria, in particular (P=0.004 and 0.003, respectively). IFNAR1 diplotypes were then constructed for these two markers using the PHASE software package. The (17470-G L168V-G/17470-G L168V-G) diplotype was found to be associated with a reduced risk of cerebral malaria and the (17470-C L168V-C/17470-G L168V-G) diplotype with an increased risk of cerebral malaria (overall 3 × 2 χ2=12.8, d.f.=2, P=0.002 and 3 × 2 χ2=15.2, d.f.=2, P=0.0005, respectively). These data suggest a role for the type I interferon pathway in resistance to cerebral malaria.

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Acknowledgements

This work was funded by the Wellcome Trust. AVSH is a Wellcome Trust Principal Research Fellow. The authors thank the many investigators involved in the original case–control study in The Gambia for their contributions.

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Authors and Affiliations

  1. Wellcome Trust Centre for Human Genetics, Henry Wellcome Building of Genomic Medicine, Roosevelt Drive, Oxford, OX3 7BN, UK

    C Aucan, A J Walley, B J W Hennig, J Fitness, A Frodsham, L Zhang, D Kwiatkowski & A V S Hill

  2. MRC Laboratories, P.O. Box 273, The Gambia

    D Kwiatkowski

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  1. C Aucan
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  2. A J Walley
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Correspondence to C Aucan.

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Aucan, C., Walley, A., Hennig, B. et al. Interferon-alpha receptor-1 (IFNAR1) variants are associated with protection against cerebral malaria in The Gambia. Genes Immun 4, 275–282 (2003). https://doi.org/10.1038/sj.gene.6363962

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