title: Combined effect of IL-10 and TGF-beta1 promoter polymorphisms as a risk factor for aspirin-intolerant asthma and rhinosinusitis.
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.
  
  
  CONCLUSIONS
  Our results suggest that IL-10 promoter polymorphisms contribute to the development of AIA and that rhinosinusitis may interact genetically with TGF-beta1.
authors.affiliation: Department of Allergy and Rheumatology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: S-H
authors.initials: SH
authors.lastname: Kim
authors.forename: E-M
authors.initials: EM
authors.lastname: Yang
authors.forename: H-N
authors.initials: HN
authors.lastname: Lee
authors.forename: B-Y
authors.initials: BY
authors.lastname: Cho
authors.forename: Y-M
authors.initials: YM
authors.lastname: Ye
authors.forename: H-S
authors.initials: HS
authors.lastname: Park
mesh_terms: D000328:Adult; D000483:Alleles; D001241:Aspirin / Q000009:adverse effects* / Q000276:immunology; D001249:Asthma / Q000235:genetics* / Q000276:immunology; D004342:Drug Hypersensitivity / Q000235:genetics* / Q000276:immunology; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D019169:Jurkat Cells; D007723:Korea; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012221:Rhinitis, Allergic, Perennial / Q000235:genetics* / Q000276:immunology; D012852:Sinusitis / Q000235:genetics* / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D001241:Aspirin