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CysLTR1 promoter polymorphism and requirement for leukotriene receptor antagonist in aspirin-intolerant asthma patients.

Kim, SH; Ye, YM; Hur, GY; Lee, SK; Sampson, AP; Lee, HY; Park, HS
Pharmacogenomics, 8(9):1143-1150, 2007
Journal Title
OBJECTIVES: Leukotriene receptor antagonists (LTRA), such as montelukast, have been used as a first-line treatment for patients with aspirin-intolerant asthma (AIA). This study evaluated associations between the clinical requirement for LTRA and genetic polymorphisms of the ALOX5, LTC4S, COX-2, CysLTR1 and TBXA2R genes in the arachidonic acid cascade in the long-term management of 89 AIA patients from a Korean population.

METHODS: Asthma control status was monitored for 1 year with maintenance medications of inhaled corticosteroid and oral LTRA, and AIA patients were classified into three groups according to the mean montelukast dose required per month to maintain asthma control for 1 year: group I (> or = 200 mg montelukast/month; n = 37), group II (5-150 mg/month; n = 25) and group III (< 5 mg/month; n = 27). Genetic polymorphisms in the arachidonic acid cascade were determined using a single-base extension method.

RESULTS: We found that there was a significant difference in the genotype frequency of the CysLTR1 promoter polymorphism -634C > T among the three groups (p = 0.007 for group I vs group II, p = 0.017 for group I vs group III), while there were no significant associations between LTRA requirements and polymorphisms of the other genes. The patients with the variant genotype (CT or TT) of the -634C = T CysLTR1 promoter polymorphism showed a higher expression level than those with the common genotype (CC).

CONCLUSION: These findings indicate that the CysLTR1 promoter polymorphism is a useful genetic marker for predicting LTRA requirements in the long-term management of AIA patients.
MeSH terms
Anti-Inflammatory Agents, Non-Steroidal/adverse effectsAspirin/adverse effects*Asthma/drug therapyChildDrug Hypersensitivity/genetics*Forced Expiratory VolumeHumansKoreaLeukotriene Antagonists/therapeutic use*Membrane Proteins/genetics*Polymorphism, Genetic*Promoter Regions, Genetic*Receptors, Leukotriene/genetics*
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
Journal Papers > Research Organization > Regional Clinical Trial Center
AJOU Authors
김, 승현허, 규영박, 해심
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