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dc.contributor.authorC. C. Khoren_US
dc.contributor.authorF. O. Vannbergen_US
dc.contributor.authorS. J. Chapmanen_US
dc.contributor.authorA. Walleyen_US
dc.contributor.authorC. Aucanen_US
dc.contributor.authorH. Lokeen_US
dc.contributor.authorN. J. Whiteen_US
dc.contributor.authorT. Petoen_US
dc.contributor.authorL. K. Khoren_US
dc.contributor.authorD. Kwiatkowskien_US
dc.contributor.authorN. Dayen_US
dc.contributor.authorA. Scotten_US
dc.contributor.authorJ. A. Berkleyen_US
dc.contributor.authorK. Marshen_US
dc.contributor.authorN. Peshuen_US
dc.contributor.authorK. Maitlanden_US
dc.contributor.authorT. N. Williamsen_US
dc.contributor.authorA. V.S. Hillen_US
dc.contributor.otherWellcome Trust Centre for Human Geneticsen_US
dc.contributor.otherMahidol Universityen_US
dc.contributor.otherNuffield Department of Clinical Medicineen_US
dc.contributor.otherNational University Hospital, Singaporeen_US
dc.contributor.otherMedical Research Council Laboratories Gambiaen_US
dc.contributor.otherCho Quan Hospitalen_US
dc.contributor.otherUniversity of Oxforden_US
dc.contributor.otherWellcome Trust Research Laboratories Nairobien_US
dc.identifier.citationGenes and Immunity. Vol.8, No.7 (2007), 570-576en_US
dc.description.abstractFour cytokine receptor genes are located on Chr21q22.11, encoding the α and α subunits of the interferon-γ receptor (IFNAR1 and IFNAR2), the β subunit of the interleukin 10 receptor (IL10RB) and the second subunit of the interferon-γ receptor (IFNGR2). We previously reported that two variants in IFNAR1 were associated with susceptibility to malaria in Gambians. We now present an extensive fine-scale mapping of the associated region utilizing 45 additional genetic markers obtained from public databases and by sequencing a 44 kb region in and around the IFNAR1 gene in 24 Gambian children (12 cases/12 controls). Within the IFNAR1 gene, a newly studied C → G single-nucleotide polymorphism (IFNAR1 272354c-g) at position -576 relative to the transcription start was found to be more strongly associated with susceptibility to severe malaria. Association was observed in three populations: in Gambian (P = 0.002), Kenyan (P = 0.022) and Vietnamese (P = 0.005) case-control studies. When all three studies were combined, using the Mantel-Haenszel test, the presence of IFNAR1 -576G was associated with a substantially elevated risk of severe malaria (N = 2444, OR = 1.38, 95% CI: 1.17-1.64; P = 1.7 × 10-4). This study builds on previous work to further highlight the importance of the type-I interferon pathway in malaria susceptibility and illustrates the utility of typing SNPs within regions of high linkage disequilibrium in multiple populations to confirm initial positive associations.en_US
dc.rightsMahidol Universityen_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.subjectImmunology and Microbiologyen_US
dc.titlePositive replication and linkage disequilibrium mapping of the chromosome 21q22.1 malaria susceptibility locusen_US
Appears in Collections:Scopus 2006-2010

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