Significant Association of ADORA3 Genetic Polymorphisms with Aspirin-Intolerant Urticaria in a Korean Population

INTRODUCTION: Aspirin-intolerant urticaria (AIU) presents with the immediate onset of urticaria after aspirin ingestion persisting for 1 to more than 6 weeks depending upon the severity. Adenosine is a potent and ubiquitous signaling nucleoside that is generated in response to cellular stress and damage and is therefore increased during episodes of tissue hypoxia and inflammation. MATERIAL AND METHODS: To investigate the biological role of adenosine A3 receptor (ADORA3) in the pathogenesis of AIU, we performed an SNP haplotype-based case-control association study in 373 AIU patients including 180 aspirin-intolerant chronic urticaria (AICU), 193 aspirin-intolerant acute urticaria (AIAU), and 178 normal controls (NC) based on the Korean population. The functional effects of genetic polymorphisms in ADORA3 were analyzed by luciferase reporter assay, electrophoretic mobility shift assay (EMSA), and real-time PCR for the mRNA expression in PBMC of AIU patients. RESULTS: The haplotype [T-1050C-564] frequency of ADORA3 gene showed significantly higher in AIAU group than in AICU and NC groups (p = 0.047, for AIAU vs. AICU; p = 0.005, for AIAU vs. NC). The transcriptional activity of -564 C allele was higher than T allele, and EMSA finding showed that NF-κB bound more tightly to the C allele sequence than to the T allele sequence by EMSA. Moreover, in PBMC obtained from AIU patients, mRNA expression of ADORA3 in patients with haplotype [T-1050C-564] showed significantly higher than those without it in dominant model (p = 0.033). CONCLUSION: These results indicate that the haplotype [T-1050C-564] of ADORA3 could affect the clinical presentation of AIAU.

Author dc:creator

• 남, 은주

Contributors dc:contributor

• 박, 해심
• 대학원 의생명과학과
• 200724286

• aspirin-hypersensitivity
• urticaria
• adenosine A3 receptor
• adenosine
• ADORA3
• Genetic polymorphism
• SNP

Language dc:language

en

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000009661
000000009661

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/2263