A base substitution in the interleukin-10 (IL-10) promoter between Sp1 and ets-1 binding sites is not associated with variation of IL-10 levels.
Interleukin 10 (IL-10) may play an important anti-inflammatory and immunoregulatory role in asthma. In this study, we investigated the role of a C to A substitution at position -627 of the IL-10 promoter, located in a necessary transcriptional region, which contains a number of putative transcriptional binding sites. The -627 nucleotide position is itself flanked by Sp-1 and ets-1 binding sites. We studied the allele frequency in 53 unrelated subjects from an admixed Caucasian, Asian and Pacific Islander group with personal or family histories of asthma. The frequency of homozygous C/C, heterozygous C/A, and homozygous A/A alleles at position -627 was 0.28, 0.44 and 0.28, respectively. In vitro assays indicated no differences between the C/C and A/A forms in binding transcriptional factors, especially Sp-1 factor, or in promoter activity. Moreover, in this selected population, there was no association between the C to A substitution and serum IL-10 levels. The mean level of IL-10 serum was determined to be 3.87 +/- 1.23 pg/ml in subjects carrying the A/A genotype, 3.47 +/- 0.57 for C/C genotype and 3.13 +/- 0.41 for the heterozygous (C/A genotype). This requires confirmation by comparing to non-asthmatic subjects. We conclude that although the -627 A allele occurs frequently (50% of alleles) in this selected group, in vitro assays and serum IL-10 levels suggest that the -627C-->A substitution represents a silent or neutral variant in the IL-10 promoter.
Jourdan-Le Saux
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C
University of Hawaii, Pacific Biomedical Research Center, 1960 East-West Road, Biomed. Rm T409, Honolulu, HI 96822, USA. claude@pbrc.hawaii.edu
Bollt
O
O
Orozco
C
C
Concepcion
J
J
Yamaga
K
K
Yamamoto
F
F
Haymer
D
D
Tam
E K
EK
D000483:Alleles; D001249:Asthma / Q000235:genetics*; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000235:genetics; D050783:Proto-Oncogene Proteins c-ets; D016329:Sp1 Transcription Factor / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic
C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D016753:Interleukin-10