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.

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.

Citation

Rees, L., Wood, N., Gillespie, K., Lai, K., Gaston, K., & Mathieson, P. (2002). The interleukin-10 – 1082 G/A polymorphism: allele frequency in different populations and functional significance. Cellular and Molecular Life Sciences, 59(3), 560-569. https://doi.org/10.1007/s00018-002-8448-0

• Journal Article Type: Article
• Acceptance Date: Jan 18, 2002
• Publication Date: 2002-03
• Deposit Date: Nov 6, 2018
• Journal: Cellular and Molecular Life Sciences
• Print ISSN: 1420-682X
• Electronic ISSN: 1420-9071
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 59
• Issue: 3
• Pages: 560-569
• DOI: https://doi.org/10.1007/s00018-002-8448-0
• Public URL: https://nottingham-repository.worktribe.com/output/1037805
• Publisher URL: https://link.springer.com/article/10.1007%2Fs00018-002-8448-0