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Combined effect of IL-10 and TGF-beta1 promoter polymorphisms as a risk factor for aspirin-intolerant asthma and rhinosinusitis.

Authors
Kim, SH; Yang, EM; Lee, HN; Cho, BY; Ye, YM; Park, HS
Citation
Allergy, 64(8):1221-1225, 2009
Journal Title
Allergy
ISSN
0105-45381398-9995
Abstract
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)-beta. The goal of this study was to investigate a gene-gene interaction between IL-10 and TGF-beta1 polymorphisms in Korean asthmatics with aspirin hypersensitivity. METHODS: Single-nucleotide polymorphism genotyping of IL-10 and TGF-beta1 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-beta1-509C/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-beta1-509C/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-beta1.
MeSH terms
AdultAllelesAspirin/adverse effects*Aspirin/immunologyAsthma/genetics*Asthma/immunologyDrug Hypersensitivity/genetics*Drug Hypersensitivity/immunologyEpistasis, GeneticFemaleGene FrequencyGenetic Predisposition to DiseaseHumansInterleukin-10/genetics*Jurkat CellsKoreaMalePolymorphism, GeneticPromoter Regions, Genetic/geneticsRhinitis, Allergic, Perennial/genetics*Rhinitis, Allergic, Perennial/immunologySinusitis/genetics*Sinusitis/immunologyTransforming Growth Factor beta1/genetics*
DOI
10.1111/j.1398-9995.2009.01989.x
PMID
19222424
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
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