title: Association of the CCR3 gene polymorphism with aspirin exacerbated respiratory disease.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Allergy and Rheumatology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Yang
authors.forename: Haet-Nim
authors.initials: HN
authors.lastname: Lee
authors.forename: Gil-Soon
authors.initials: GS
authors.lastname: Choi
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Ye
authors.forename: Hae-Sim
authors.initials: HS
authors.lastname: Park
mesh_terms: D000328:Adult; D001241:Aspirin / Q000009:adverse effects / Q000276:immunology*; D016022:Case-Control Studies; D004342:Drug Hypersensitivity / Q000235:genetics* / Q000276:immunology; D005260:Female; D005787:Gene Frequency / Q000235:genetics / Q000276:immunology; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D054397:Receptors, CCR3 / Q000235:genetics*; D012120:Respiration Disorders / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology; D014581:Urticaria / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology
chemical_list: C515350:CCR3 protein, human; D005819:Genetic Markers; D054397:Receptors, CCR3; D001241:Aspirin