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Functional variability of the adenosine A3 receptor ( ADORA3 ) gene polymorphism in aspirin‐induced urticaria
Author(s) -
Kim S.H.,
Nam E.J.,
Kim Y.K.,
Ye Y.M.,
Park H.S.
Publication year - 2010
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.2010.09983.x
Subject(s) - haplotype , histamine , biology , histamine n methyltransferase , allele , microbiology and biotechnology , population , electrophoretic mobility shift assay , adenosine , gene expression , gene , receptor , genetics , medicine , endocrinology , histamine h2 receptor , environmental health , antagonist
Summary Background To improve understanding of aspirin hypersensitivity, this study focused on adenosine as a noncyclooxygenase target molecule of aspirin. Adenosine may affect the release of histamine from cutaneous mast cells through a mechanism mediated by the adenosine A3 receptor. Objectives To investigate the genetic contribution of adenosine A3 receptor gene ( ADORA3 ) polymorphisms in the pathogenesis of aspirin‐induced urticaria (AIU) in a case–control association study in a Korean population. Methods A case–control association study was performed in 385 patients with AIU and 213 normal controls from a Korean population. The functional variability of genetic polymorphisms in the ADORA3 gene was analysed in in vitro studies that included a luciferase reporter assay and an electrophoretic mobility shift assay (EMSA), and ex vivo studies that included real‐time polymerase chain reaction for mRNA expression in peripheral blood mononuclear cells and a histamine release assay. Results A significant association of ADORA3 promoter polymorphism at −1050G/T was found with the phenotype of AIU. Patients with AIU showed higher frequency of the haplotype, ht1 (T −1050 C −564 ), compared with normal healthy controls. Moreover, ht1 (TC) was found to be a high‐transcript haplotype by the luciferase activity assay, and a −564C allele‐specific DNA binding protein was found by EMSA. Increased basophil histamine release was noted in subjects who had the high‐transcript haplotype, ht1 (TC). Conclusion These results suggest that the high‐transcript haplotype, ht1 (TC), of the ADORA3 gene may contribute to the development of cutaneous hyper‐reactivity to aspirin, leading to the clinical presentation of AIU.