Significant association of FcepsilonRIalpha promoter polymorphisms with aspirin-intolerant chronic urticaria.
Bae, JS; Kim, SH; Ye, YM; Yoon, HJ; Suh, CH; Nahm, DH; Park, HS
The Journal of allergy and clinical immunology, 119(2):449-456, 2007
The Journal of allergy and clinical immunology
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.
CONCLUSION: 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.
CLINICAL IMPLICATIONS: The FcepsilonRIalpha -344C>T polymorphism may contribute to the development of AICU.
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