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

2006; Wiley; Volume: 36; Issue: 4 Linguagem: Inglês

10.1111/j.1365-2222.2006.02457.x

1365-2222

Seung‐Hyun Kim, Jae‐Min Oh, Younghoon Kim, Lyle J. Palmer, Chang‐Hee Suh, Dong‐Ho Nahm, Hae‐Sim Park,

Mast cells and histamine

Summary 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.