Cysteinyl leukotriene receptor 1 promoter polymorphism is associated with aspirin-intolerant asthma in malesopen access
- Authors
- Kim, Seung-Hyun; Oh, Jay Min; Kim, Yongseok; Palmer, Lyle John; Suh, Chang-Hee; Nahm, Dong-Ho; Park, Hae-Sim
- Issue Date
- Apr-2006
- Publisher
- WILEY-BLACKWELL
- Keywords
- aspirin-intolerant asthma; cysteinyl leukotriene receptor 1; single nucleotide polymorphism
- Citation
- CLINICAL AND EXPERIMENTAL ALLERGY, v.36, no.4, pp.433 - 439
- Indexed
- SCIE
SCOPUS
- Journal Title
- CLINICAL AND EXPERIMENTAL ALLERGY
- Volume
- 36
- Number
- 4
- Start Page
- 433
- End Page
- 439
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/181594
- DOI
- 10.1111/j.1365-2222.2006.02457.x
- ISSN
- 0954-7894
- 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.
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