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  • Original Article
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Interferon regulatory factor-1 polymorphisms are associated with the control of Plasmodium falciparum infection

Genes & Immunity volume 9, pages 122–129 (2008)Cite this article

A Corrigendum to this article was published on 23 July 2008

Abstract

We describe the haplotypic structure of the interferon regulatory factor-1 (IRF-1) locus in two West African ethnic groups, Fulani and Mossi, that differ in their susceptibility and immune response to Plasmodium falciparum malaria. Both populations showed significant associations between IRF-1 polymorphisms and carriage of P. falciparum infection, with different patterns of association that may reflect their different haplotypic architecture. Genetic variation at this locus does not therefore account for the Fulani-specific resistance to malaria while it could contribute to parasite clearance's ability in populations living in endemic areas. We then conducted a case–control study of three haplotype-tagging single nucleotide polymorphisms (htSNPs) in 370 hospitalised malaria patients (160 severe and 210 uncomplicated) and 410 healthy population controls, all from the Mossi ethnic group. All three htSNPs showed correlation with blood infection levels in malaria patients, and the rs10065633 polymorphism was associated with severe disease (P=0.02). These findings provide the first evidence of the involvement in malaria susceptibility of a specific locus within the 5q31 region, previously shown to be linked with P. falciparum infection levels.

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Acknowledgements

We dedicate this work to the memory of our dear friend and colleague Dr G Luoni, whom we really miss and we would love to keep discussing the data with. We are grateful to the villagers of Barkoumbilen and Barkoundouba, as well as to the hospitalised children and their families, for their very kind collaboration and participation to this study. We are deeply indebted to the personnel of the Immuno-parasitology Unit of the Centre National del Rechèrche et Formation sur le Paludisme of Ouagadougou, Burkina Faso. We thank Dr A Morris for statistical support, Dr Federica Verra for critical review of the manuscript and Professor Marita Troye-Blomberg for useful discussions and supervision of VD Mangano's PhD work. The study was supported by the EU, Sixth Framework Programme, BIOMALPAR Network of Excellence, contract number LSHP-CT-2004-503578, by the Italian Ministry for University and Research (MIUR COFIN, 2003, 2006), by the Istituto Pasteur—Fondazione Cenci Bolognetti of the University of Rome ‘La Sapienza’ and by the UK Medical Research Council.

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Authors and Affiliations

  1. Dipartimento di Scienze di Sanità Pubblica, Sezione di Parassitologia, Università di Roma ‘La Sapienza’, Rome, Italy

    V D Mangano, G Luoni, G Bancone & D Modiano

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

    V D Mangano, G Luoni, K A Rockett, J Forton, T G Clark, E S Akha & D P Kwiatkowski

  3. Centre National de Rechèrche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso

    B S Sirima & A Konaté

  4. Wellcome Trust Sanger Institute, Hinxton, UK

    D P Kwiatkowski

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  1. V D Mangano
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  2. G Luoni
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  3. K A Rockett
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  4. B S Sirima
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Correspondence to D Modiano.

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Mangano, V., Luoni, G., Rockett, K. et al. Interferon regulatory factor-1 polymorphisms are associated with the control of Plasmodium falciparum infection. Genes Immun 9, 122–129 (2008). https://doi.org/10.1038/sj.gene.6364456

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  • DOI: https://doi.org/10.1038/sj.gene.6364456

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