Document Detail


Genetic variability in CRTH2 polymorphism increases eotaxin-2 levels in patients with aspirin exacerbated respiratory disease.
MedLine Citation:
PMID:  19796209     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
INTRODUCTION: CRTH2 is expressed on the surface of eosinophils and has been shown to mediate PGD2-induced eosinophil migration in vitro. Eosinophilic infiltration in the upper and lower airways is the key feature of asthma. Considering the fact that eosinophil infiltration is prominent in the upper and lower airways of aspirin exacerbated respiratory disease (AERD) compared to aspirin-tolerant asthma (ATA) patients, we hypothesized that activation of eosinophils via dysregulation of the CRTH2 gene may play an important role and be an important marker for AERD. METHODS: The three study groups - 107 with AERD, 115 with ATA and 133 normal healthy controls (NC) - were recruited from Ajou University Hospital, South Korea. Two polymorphisms of the CRTH2 gene at -466T>C and -129C>A were genotyped using primer extension methods. RESULTS: AERD patients had significantly higher serum eotaxin-2 levels than did those with ATA (P = 0.034). A significant difference in the genotype frequencies of CRTH2 -466T>C was detected between AERD and ATA patients (P < 0.05). The serum eotaxin-2 level was significantly higher in AERD patients carrying the TT genotype of CRTH2 -466T>C than those with the CT and CC (P < 0.05). In vitro functional study demonstrated that the -466T allele had lower luciferase activity (P < 0.001) and lower mRNA expression with higher production of eotaxin-2 (P = 0.003) in human lung epithelial cells. EMSA showed that CRTH2 -466T produced a specific band with a higher affinity than CRTH2 -466C had. CONCLUSION: The CRTH2 -466T>C polymorphism increases serum and cellular eotaxin-2 production through lowered CRTH2 expression, leading to eosinophilic infiltration in AERD patients.
Authors:
N S Palikhe; S-H Kim; B-Y Cho; Y-M Ye; G-S Choi; H-S Park
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-10-01
Journal Detail:
Title:  Allergy     Volume:  65     ISSN:  1398-9995     ISO Abbreviation:  Allergy     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-04-27     Completed Date:  2010-08-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7804028     Medline TA:  Allergy     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  338-46     Citation Subset:  IM    
Affiliation:
Department of Allergy & Rheumatology, Ajou University School of Medicine, Suwon, South Korea.
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MeSH Terms
Descriptor/Qualifier:
Adult
Asthma, Aspirin-Induced / genetics*,  immunology*,  metabolism
Chemokine CCL24 / biosynthesis*,  genetics,  immunology
Electrophoretic Mobility Shift Assay
Enzyme-Linked Immunosorbent Assay
Eosinophils / immunology,  metabolism
Female
Genetic Predisposition to Disease
Humans
Male
Middle Aged
Polymerase Chain Reaction
Polymorphism, Single Nucleotide
Receptors, Immunologic / genetics*
Receptors, Prostaglandin / genetics*
Chemical
Reg. No./Substance:
0/Chemokine CCL24; 0/Receptors, Immunologic; 0/Receptors, Prostaglandin; 0/prostaglandin D2 receptor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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