A novel polymorphic GATA site in the human IL-12Rbeta2 promoter region affects transcriptional activity
| Autor: | René E. Jonkers, R. Van Den Bogaard, A. van Veen, Eddy A. Wierenga, Robert Westland, T.C.T.M. (Tineke) van der Pouw Kraan, J.G.I. van Rietschoten, M.A. Nieste-Otter, M.T. den Hartog |
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| Přispěvatelé: | Amsterdam institute for Infection and Immunity, Pulmonology, Cell Biology and Histology |
| Rok vydání: | 2004 |
| Předmět: |
Consensus site
5' Flanking Region Immunology Population Molecular Sequence Data Single-nucleotide polymorphism Biology Biochemistry Polymorphism Single Nucleotide Consensus Sequence Genetics Immunology and Allergy Coding region Humans education Promoter Regions Genetic Gene education.field_of_study Base Sequence GATA2 GATA3 Receptors Interleukin-12 Promoter General Medicine Receptors Interleukin Molecular biology Asthma |
| Zdroj: | Tissue antigens, 63(6), 538-546. Wiley-Blackwell |
| ISSN: | 0001-2815 |
| Popis: | Interleukin-12 (IL-12) is a potent inducer of interferon-gamma production by T cells and is a major factor for the development of T-helper 1 (Th1) cells. It exerts its biological effects through binding to the IL-12 receptor (IL-12R), a heterodimer composed of a 1 and a beta2 subunits. The signaling beta2 chain is expressed on Th1 cells and to a lesser extent on Th0 cells, but not on Th2 cells, rendering these latter cells unresponsive to IL-12. Polymorphisms in the coding region of the IL-12Rbeta2 gene were shown to be associated with atopic disease. Here, we analyzed the 5'-regulatory region of the human IL-12Rbeta2 gene by denaturing high-performance liquid chromatography (Transgenomic WAVE system, San Jose, CA). We found five novel single-nucleotide polymorphisms (SNPs) in the proximal 1.2 kb IL-12Rbeta2 promoter region, i.e. -237C/T, -465A/G, -1023A/G, -1033T/C, and -1035A/G. SNP -465A/G is of particular interest as it determines the integrity of a GATA consensus site. By functional comparison of both -465 alleles in transient transfection assays, we show that promoter activity is increased in case of the -465G allele, disrupting the intact GATA site. Comparison of the prevalence of -465A/G SNP alleles in small cohorts of allergic asthmatic and healthy control individuals provided no evidence for an altered distribution in the asthmatic population. In conclusion, we have identified a novel polymorphic GATA site that may affect transciptional activity of the human IL-12Rbeta2 gene under GATA3-mediated, Th2-polarizing conditions. |
| Databáze: | OpenAIRE |
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