title: A novel polymorphic GATA site in the human IL-12Rbeta2 promoter region affects transcriptional activity.
abstract: 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.
authors.affiliation: Department of Cell Biology & Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. jgi.vanrietschoten@vumc.nl
authors.forename: J G I
authors.initials: JG
authors.lastname: van Rietschoten
authors.forename: R
authors.initials: R
authors.lastname: Westland
authors.forename: R
authors.initials: R
authors.lastname: van den Bogaard
authors.forename: M A
authors.initials: MA
authors.lastname: Nieste-Otter
authors.forename: A
authors.initials: A
authors.lastname: van Veen
authors.forename: R E
authors.initials: RE
authors.lastname: Jonkers
authors.forename: T C T M
authors.initials: TC
authors.lastname: van der Pouw Kraan
authors.forename: M T
authors.initials: MT
authors.lastname: den Hartog
authors.forename: E A
authors.initials: EA
authors.lastname: Wierenga
mesh_terms: D024506:5' Flanking Region; D001249:Asthma / Q000235:genetics; D001483:Base Sequence; D016384:Consensus Sequence; D006801:Humans; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D018123:Receptors, Interleukin / Q000235:genetics*; D053707:Receptors, Interleukin-12
chemical_list: C508439:IL12RB2 protein, human; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12