Significant association of FcɛRIα promoter polymorphisms with aspirin-intolerant chronic urticaria

BackgroundAlthough 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).ObjectiveWe investigated whether genetic polymorphisms on the α-chain of the high-affinity IgE receptor (FcɛRIα) gene were associated with the AICU phenotype.MethodsWe genotyped 2 promoter polymorphisms (−344C>T and −95T>C) of FcɛRIα 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.ResultsThe 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.ConclusionThese results suggest that the −344C>T polymorphism of the FcɛRIα promoter may be associated with increased expression of FcɛRIα on mast cells and enhanced release of histamine.Clinical implicationsThe FcɛRIα −344C>T polymorphism may contribute to the development of AICU.