The interleukin-10-1082 G/A polymorphism: allele frequency in different populations and functional significance
| Autor: | Kevin Gaston, Kathleen M Gillespie, Len Rees, KM Lai, PW Mathieson, N. A. P. Wood |
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| Rok vydání: | 2002 |
| Předmět: |
Adult
Male Adolescent Genotype Transcription Genetic Electrophoretic Mobility Shift Assay Enzyme-Linked Immunosorbent Assay Biology Response Elements Transfection Peripheral blood mononuclear cell Cellular and Molecular Neuroscience Gene Frequency Humans Allele Promoter Regions Genetic Molecular Biology Allele frequency Transcription factor Cells Cultured Aged Pharmacology Regulation of gene expression Genetics Reporter gene B-Lymphocytes Binding Sites Polymorphism Genetic Nuclear Proteins Cell Biology Middle Aged Molecular biology Interleukin-10 DNA-Binding Proteins Gene Expression Regulation Leukocytes Mononuclear Molecular Medicine Female Transcription Factors |
| Zdroj: | Cellular and molecular life sciences : CMLS. 59(3) |
| ISSN: | 1420-682X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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