Abstract
We analyzed a single nucleotide polymorphism (SNP) at position −56 (T→C) in the promoter region of the gene encoding the human interferon-gamma receptor ligand-binding chain I (IFN-γR1). The mutation was present at similar frequencies in Gabonese children with either mild or severe malaria. Functional investigations of the promoter in a transfected human B-cell line showed lower levels of luciferase reporter gene expression in the presence of the mutation, indicating the importance of this position for promoter activity, and suggesting that this SNP might negatively influence the expression level of IFN-γR1 at the cell surface. Further examinations of the DNA sequence at this polymorphic site showed a perfectly matched binding site for the transcription factor activator protein 4 (AP-4) on both strands. Binding sites for other important transcription factors involved in gene expression and regulation of the immune response against infections, including Ikaros 2 (Ik-2), nuclear factor κB (NFκB), and CETS1p54, are also situated in this region.
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Acknowledgements
We are thankful for financial support from the fortüne program (734-1-0) of the Medical Faculty of the Universitätsklinikum Tübingen and the National Genome Research Network supported by the Bundesministerium für Bildung und Forschung (01GS0114). We also thank S. Grummes and A. Weierich for technical assistance. Ethical clearance was given by the ethics committee of the International Foundation of the Albert Schweitzer Hospital in Lambaréné.
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HGBASE accession number: SNP000064373
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Jüliger, S., Bongartz, M., Luty, A.J.F. et al. Functional analysis of a promoter variant of the gene encoding the interferon-gamma receptor chain I. Immunogenetics 54, 675–680 (2003). https://doi.org/10.1007/s00251-002-0516-y
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DOI: https://doi.org/10.1007/s00251-002-0516-y