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The interleukin-10 – 1082 G/A polymorphism: allele frequency in different populations and functional significance

Rees, L.E.N.; Wood, N.A.P.; Gillespie, K.M.; Lai, K.N.; Gaston, K.; Mathieson, P.W.

Authors

L.E.N. Rees

N.A.P. Wood

K.M. Gillespie

K.N. Lai

K. Gaston

P.W. Mathieson

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.

Journal Article Type Article
Publication Date 2002-03
Journal Cellular and Molecular Life Sciences
Print ISSN 1420-682X
Publisher BMC
Peer Reviewed Peer Reviewed
Volume 59
Issue 3
Pages 560-569
DOI https://doi.org/10.1007/s00018-002-8448-0
Publisher URL https://link.springer.com/article/10.1007%2Fs00018-002-8448-0

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