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Association of the CCR3 gene polymorphism with aspirin exacerbated respiratory disease.

Authors
Kim, SH; Yang, EM; Lee, HN; Choi, GS; Ye, YM; Park, HS
Citation
Respiratory medicine, 104(5):626-632, 2010
Journal Title
Respiratory medicine
ISSN
0954-61111532-3064
Abstract
INTRODUCTION: Aspirin hypersensitivity represents two distinct clinical syndromes, such as aspirin exacerbated respiratory disease (AERD) and aspirin-intolerant chronic urticaria/angioedema (AICU) which have different clinical phenotypes resulting from different genetic backgrounds in a Korean population. Persistent eosinophilic inflammation in airway is a characteristic feature of AERD and chemokine CC motif receptor 3 (CCR3) plays an important role in eosinophilic infiltration into the asthmatic airway. OBJECTIVES: The main objective of this study is to investigate the association between CCR3 gene polymorphisms and aspirin hypersensitivity, including AERD and AICU. METHODS: CCR3 mRNA expression was measured after an aspirin provocation test by real-time PCR. In total, 330 patients with aspirin hypersensitivity (191 AERD and 139 AICU) and 217 normal healthy controls (NC) were genotyped for two CCR3 promoter polymorphisms (-520T/G and -174C/T), and the functional effects of the polymorphisms were analyzed applying a luciferase reporter assay and an electrophoretic mobility shift assay. RESULTS: CCR3 mRNA expression was significantly increased after aspirin provocation in AERD patients (P=0.002) but not in AICU patients. An in vitro functional study showed that the reporter construct having a -520G allele exhibited significantly higher promoter activity compared with the construct having a -520T allele in human myeloid (U937), lymphoid (Jurkat), and mast (HMC-1) cell lines (P<0.001). We found -520G and -174T specific bands on EMSA. CONCLUSION: This result suggests that the CCR3 genetic polymorphisms may contribute to the development of the AERD phenotype and may be used as a genetic marker for differentiating between the two major aspirin hypersensitivity phenotypes.
MeSH terms
AdultAspirin/adverse effects/*immunologyCase-Control StudiesDrug Hypersensitivity/*genetics/immunologyFemaleGene Frequency/genetics/immunologyGenetic MarkersGenotypeHumansMalePhenotype*Polymorphism, GeneticReceptors, CCR3/*geneticsRespiration Disorders/chemically induced/*genetics/immunologyUrticaria/chemically induced/*genetics/immunology
DOI
10.1016/j.rmed.2009.11.024
PMID
20022477
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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