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Cysteinyl leukotriene receptor 1 promoter polymorphism is associated with aspirin-intolerant asthma in males.

Authors
Kim, SH; Oh, JM; Kim, YS; Palmer, LJ; Suh, CH; Nahm, DH; Park, HS
Citation
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 36(4):433-439, 2006
Journal Title
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
ISSN
0954-78941365-2222
Abstract
BACKGROUND: Cysteinyl leukotrienes (CysLTs) play important roles in the pathogenesis of eosinophilic airway inflammation characterized by bronchoconstriction, mucus secretion and airway hyper-responsiveness via cysteinyl leukotriene receptor 1 (CysLTR1)-mediated mechanism. CysLTR1-selective antagonists have anti-bronchoconstrictive and anti-inflammatory effects in asthma, particularly aspirin-intolerant asthma (AIA).



METHODS: To investigate the association of CysLTR1 with AIA development, we identified three single nucleotide polymorphisms (SNPs), -634C>T, -475A>C, -336A>G, in the 5' upstream region of CysLTR1 gene using a direct sequencing method in 105 AIA patients, 110 ASA-tolerant asthma (ATA) patients and 125 normal healthy controls (NC).



RESULTS: Significant differences were observed in allele frequencies of the three SNPs within male subjects; Male AIA patients had higher frequencies of the minor alleles of these three SNPs than male control groups (P=0.03 for AIA vs. NC; P=0.02 for AIA vs. ATA). Moreover, three-SNP haplotype, ht2 [T-C-G], was associated with increased disease risk (odds ratio (OR)=2.71, P=0.03 for AIA vs. NC; OR=2.89, P=0.02 for AIA vs. ATA) in males. CysLTR1 haplotypes were also associated with altered gene expression; luciferase activity was significantly enhanced with the ht2 [T-C-G] construct in comparison with the ht1 [C-A-A] construct in human Jurkat cells (P=0.04).



CONCLUSION: These results suggest that genetic variants of CysLTR1 are associated with AIA in a Korean population, and may modulate CysLTR1 expression.
MeSH terms
AdultAllelesAnti-Inflammatory Agents, Non-Steroidal/immunology*Aspirin/immunology*Asthma/genetics*Asthma/immunologyCase-Control StudiesDrug Hypersensitivity/genetics*Drug Hypersensitivity/immunologyFemaleGene FrequencyHaplotypesHumansMaleMembrane Proteins/genetics*Membrane Proteins/immunologyMiddle AgedPhenotypePolymorphism, Single Nucleotide/genetics*Polymorphism, Single Nucleotide/immunologyPromoter Regions, Genetic/geneticsPromoter Regions, Genetic/immunologyReceptors, Leukotriene/genetics*Receptors, Leukotriene/immunologySex FactorsTranscription, Genetic/geneticsTranscription, Genetic/immunology
DOI
10.1111/j.1365-2222.2006.02457.x
PMID
16630147
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
Journal Papers > Research Organization > Regional Clinical Trial Center
Journal Papers > School of Medicine / Graduate School of Medicine > Rheumatology
AJOU Authors
김, 승현서, 창희남, 동호박, 해심
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