Abstract.
Genotypic variation in the human interleukin-10 (IL-10) promoter may account for marked inter-individual variation in IL-10 production and may influence susceptibility to autoimmune diseases. The G/A polymorphism at position -1082 has been linked to high/low IL-10 producer status. We directly tested the functional significance of this polymorphism using DNA-binding assays and reporter gene assays, examined allele frequencies in two geographically distinct populations and assessed intra- and inter-individual variation in IL-10 production in vitro according to genotype. Functional analyses showed that the -1082 region contains a putative ETS-like transcription factor-binding site, and nuclear factors from a monocyte cell line bind to this region. Transient transfection studies in an Epstein-Barr virus-transformed B cell line indicated that the -1082 A allele confers a two fold increase in transcriptional activity of the IL-10 promoter compared to the G allele. There was marked inter-individual variation in IL-10 production by peripheral blood mononuclear cells in vitro, with no consistent effect of genotype.
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Received 26 October 2001; received after revision 21 December 2001; accepted 18 January 2002
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Rees, L., Wood, N., Gillespie, K. et al. The interleukin-10 - 1082 G/A polymorphism: allele frequency in different populations and functional significance. CMLS, Cell. Mol. Life Sci. 59, 560–569 (2002). https://doi.org/10.1007/s00018-002-8448-0
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DOI: https://doi.org/10.1007/s00018-002-8448-0