Publication: Positive replication and linkage disequilibrium mapping of the chromosome 21q22.1 malaria susceptibility locus
Issued Date
2007-10-01
Resource Type
ISSN
14765470
14664879
14664879
Other identifier(s)
2-s2.0-35548985384
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Genes and Immunity. Vol.8, No.7 (2007), 570-576
Suggested Citation
C. C. Khor, F. O. Vannberg, S. J. Chapman, A. Walley, C. Aucan, H. Loke, N. J. White, T. Peto, L. K. Khor, D. Kwiatkowski, N. Day, A. Scott, J. A. Berkley, K. Marsh, N. Peshu, K. Maitland, T. N. Williams, A. V.S. Hill Positive replication and linkage disequilibrium mapping of the chromosome 21q22.1 malaria susceptibility locus. Genes and Immunity. Vol.8, No.7 (2007), 570-576. doi:10.1038/sj.gene.6364417 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/24114
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Title
Positive replication and linkage disequilibrium mapping of the chromosome 21q22.1 malaria susceptibility locus
Abstract
Four 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.