The interleukin-10-1082 G/A polymorphism: allele frequency in different populations and functional significance.
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.
Rees
L E N
LE
Academic Renal Unit, Southmead Hospital, Bristol, United Kingdom.
Wood
N A P
NA
Gillespie
K M
KM
Lai
K N
KN
Gaston
K
K
Mathieson
P W
PW
D000293:Adolescent; D000328:Adult; D000368:Aged; D001402:B-Lymphocytes; D001665:Binding Sites; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency / Q000235:genetics*; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics*; D007963:Leukocytes, Mononuclear; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020218:Response Elements / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D014162:Transfection
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D016753:Interleukin-10