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


Dr Hae-Sim Park, Department of Allergy and Rheumatology, Ajou University School of Medicine, San-5, Wonchondong, Paldalgu, Suwon, Korea.


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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