Functional variability of the adenosine A3 receptor (ADORA3) gene polymorphism in aspirin-induced urticaria
SCIE
SCOPUS
- Title
- Functional variability of the adenosine A3 receptor (ADORA3) gene polymorphism in aspirin-induced urticaria
- Authors
- Kim, SH; Nam, EJ; Kim, YK; Ye, YM; Park, HS
- Date Issued
- 2010-11
- Publisher
- "WILEY-BLACKWELL PUBLISHING, INC"
- Abstract
- 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.
- Keywords
- adenosine; adenosine A3 receptor; aspirin hypersensitivity; genetic polymorphism; urticaria; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; INTOLERANT CHRONIC URTICARIA; MAST-CELLS; A(3) RECEPTOR; INDUCED ASTHMA; IN-VITRO; KAPPA-B; DEGRANULATION; ACTIVATION; RELEASE
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/25285
- DOI
- 10.1111/J.1365-2133.2010.09983.X
- ISSN
- 0007-0963
- Article Type
- Article
- Citation
- BRITISH JOURNAL OF DERMATOLOGY, vol. 163, no. 5, page. 977 - 985, 2010-11
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