Combined effect of IL-10 and TGF-β1 promoter polymorphisms as a risk factor for aspirin-intolerant asthma and rhinosinusitis
June 26th, 2009 Posted by: admin
Background: It has been known that interleukin (IL)-10 promoter polymorphisms at [minus]1082A/G, [minus]819T/C and [minus]592A/C, may influence IL-10 expression and associate with asthma. Interleukin-10 facilitates the regulatory function of transforming growth factor (TGF)-[beta]. The goal of this study was to investigate a gene[ndash]gene interaction between IL-10 and TGF-[beta]1 polymorphisms in Korean asthmatics with aspirin hypersensitivity.Methods: Single-nucleotide polymorphism genotyping of IL-10 and TGF-[beta]1 genes was performed and the functional effect of the IL-10 polymorphisms was analysed applying a luciferase reporter assay and an electrophoretic mobility shift assay.Results: Among the patients with asthma, polymorphism at [minus]1082A/G was significantly associated with the phenotype of aspirin-intolerant asthma, AIA (P = 0.007, Pc = 0.021). Moreover, a synergistic effect between the TGF-[beta]1[minus]509C/T and IL-10[minus]1082A/G polymorphisms on the phenotype of AIA was noted; when stratified by the presence of rhinosinusitis, the frequency of rare alleles (the CT or TT genotype of TGF-[beta]1[minus]509C/T and AG or GG genotype of IL-10[minus]1082A/G) was significantly higher in the patients with AIA (15.2%) when compared with those with ATA (6.3%, P = 0.031; odds ratio 4.111; 95% confidence interval 1.504[ndash]11.235). In an in vitro functional assay, the [minus]1082G reporter plasmid exhibited significantly greater promoter activity when compared with the [minus]1082A construct in Jurkat T cells (P = 0.011). Moreover, we found that the transcription factor Myc-associated zinc-finger protein preferentially bound the [minus]1082G allele.Conclusion: Our results suggest that IL-10 promoter polymorphisms contribute to the development of AIA and that rhinosinusitis may interact genetically with TGF-[beta]1.
