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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
Citation
The British journal of dermatology, 163(5):977-985, 2010
Journal Title
The British journal of dermatology
ISSN
0007-09631365-2133
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.
MeSH terms
AdultAnti-Inflammatory Agents, Non-Steroidal/*adverse effectsAsian Continental Ancestry Group/geneticsAspirin/*adverse effectsBasophils/metabolismCase-Control StudiesDrug Hypersensitivity/*geneticsElectrophoretic Mobility Shift AssayFemaleGene FrequencyGenetic Predisposition to DiseaseGenetic VariationHistamine/metabolismHumansKoreaMaleMiddle AgedPolymerase Chain Reaction/methods*Polymorphism, GeneticReceptor, Adenosine A2B/geneticsReceptor, Adenosine A3/*geneticsUrticaria/*chemically induced/*genetics/metabolism
DOI
10.1111/j.1365-2133.2010.09983.x
PMID
20716228
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
Journal Papers > Research Organization > Regional Clinical Trial Center
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