title: Significant association of FcepsilonRIalpha promoter polymorphisms with aspirin-intolerant chronic urticaria.
abstract: BACKGROUND
  Although the mechanism that underlies aspirin hypersensitivity is not completely understood, an IgE-mediated response was reported for a patient with aspirin-intolerant chronic urticaria (AICU).
  
  
  OBJECTIVE
  We investigated whether genetic polymorphisms on the alpha-chain of the high-affinity IgE receptor (FcepsilonRIalpha) gene were associated with the AICU phenotype.
  
  
  METHODS
  We genotyped 2 promoter polymorphisms (-344C>T and -95T>C) of FcepsilonRIalpha gene in the Korean population, and the functional effect of the -344C>T polymorphism was analyzed by using a luciferase reporter assay and an electrophoretic mobility shift assay.
  
  
  RESULTS
  The rare allele frequency of the -344C>T polymorphism was significantly higher in the patients with AICU compared with the other subjects (P= .008 for AICU vs aspirin-tolerant chronic urticaria; P= .03 for AICU vs controls). This polymorphism was also significantly associated with total serum IgE concentrations and a higher rate of atopy in the patients with AICU (P= .01 and .05, respectively). The reporter plasmid that carried the -344T allele exhibited significantly higher promoter activity in a rat mast cell line (RBL-2H3) compared with the promoter activity of the -344C allele (P< .001). We found that transcription factor Myc-associated zinc finger protein preferentially bound the -344C promoter. Moreover, patients with AICU with the heterozygous CT genotype of the -344C>T polymorphism exhibited greater anti-IgE-mediated histamine release compared with those with the homozygous CC genotype.
  
  
  CONCLUSIONS
  These results suggest that the -344C>T polymorphism of the FcepsilonRIalpha promoter may be associated with increased expression of FcepsilonRIalpha on mast cells and enhanced release of histamine.
  
  
  CONCLUSIONS
  The FcepsilonRIalpha -344C>T polymorphism may contribute to the development of AICU.
authors.affiliation: Department of Allergy and Rheumatology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Jin-Sik
authors.initials: JS
authors.lastname: Bae
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Ye
authors.forename: Ho Joo
authors.initials: HJ
authors.lastname: Yoon
authors.forename: Chang-Hee
authors.initials: CH
authors.lastname: Suh
authors.forename: Dong-Ho
authors.initials: DH
authors.lastname: Nahm
authors.forename: Hae-Sim
authors.initials: HS
authors.lastname: Park
mesh_terms: D001241:Aspirin / Q000009:adverse effects*; D001491:Basophils / Q000378:metabolism; D002908:Chronic Disease; D004268:DNA-Binding Proteins / Q000502:physiology; D004342:Drug Hypersensitivity / Q000235:genetics*; D006636:Histamine Release; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D017455:Receptors, IgE / Q000235:genetics*; D014157:Transcription Factors / Q000502:physiology; D014581:Urticaria / Q000209:etiology / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C475664:FCER1A protein, human; D017455:Receptors, IgE; D014157:Transcription Factors; C076035:c-MYC-associated zinc finger protein; D001241:Aspirin