A novel polymorphic GATA site in the human IL‐12Rβ2 promoter region affects transcriptional activity

Abstract: Interleukin‐12 (IL‐12) is a potent inducer of interferon‐γ 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 β2 subunits. The signaling β2 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‐12Rβ2 gene were shown to be associated with atopic disease. Here, we analyzed the 5′‐regulatory region of the human IL‐12Rβ2 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‐12Rβ2 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‐12Rβ2 gene under GATA3‐mediated, Th2‐polarizing conditions.