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Combined effect of IL‐10 and TGF‐β1 promoter polymorphisms as a risk factor for aspirin‐intolerant asthma and rhinosinusitis
Author(s) -
Kim S.H.,
Yang E.M.,
Lee H.N.,
Cho B.Y.,
Ye Y.M.,
Park H.S.
Publication year - 2009
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/j.1398-9995.2009.01989.x
Subject(s) - asthma , genotype , allele , medicine , odds ratio , immunology , single nucleotide polymorphism , aspirin , genotyping , promoter , transforming growth factor , interleukin , microbiology and biotechnology , gene , biology , genetics , gene expression , cytokine
Background: It has been known that interleukin (IL)‐10 promoter polymorphisms at −1082A/G, −819T/C and −592A/C, may influence IL‐10 expression and associate with asthma. Interleukin‐10 facilitates the regulatory function of transforming growth factor (TGF)‐β. The goal of this study was to investigate a gene–gene interaction between IL‐10 and TGF‐β1 polymorphisms in Korean asthmatics with aspirin hypersensitivity. Methods: Single‐nucleotide polymorphism genotyping of IL‐10 and TGF‐β1 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 −1082A/G was significantly associated with the phenotype of aspirin‐intolerant asthma, AIA ( P = 0.007, P c = 0.021). Moreover, a synergistic effect between the TGF‐β1 −509C/T and IL‐10 −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‐β1 −509C/T and AG or GG genotype of IL‐10 −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 1.504–11.235). In an in vitro functional assay, the −1082G reporter plasmid exhibited significantly greater promoter activity when compared with the −1082A construct in Jurkat T cells ( P = 0.011). Moreover, we found that the transcription factor Myc‐associated zinc‐finger protein preferentially bound the −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‐β1 .