TY - JOUR
T1 - Cysteinyl leukotriene receptor 1 promoter polymorphism is associated with aspirin-intolerant asthma in males
AU - Kim, S.H.
AU - Oh, J.M.
AU - Kim, Y.S.
AU - Palmer, Lyle
AU - Suh, C.H.
AU - Nahm, D.H.
AU - Park, H.S.
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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.
U2 - 10.1111/j.1365-2222.2006.02457.x
DO - 10.1111/j.1365-2222.2006.02457.x
M3 - Article
VL - 36
SP - 433
EP - 439
JO - Clinical & Experimental Allergy
JF - Clinical & Experimental Allergy
SN - 0954-7894
IS - 4
ER -