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- Title
TBXA2R gene polymorphism and responsiveness to leukotriene receptor antagonist in children with asthma.
- Authors
Kim, J-H.; Lee, S-Y.; Kim, H-B.; Jin, H-S.; Yu, J-H.; Kim, B-J.; Kim, B-S.; Kang, M-J.; Jang, S-O.; Hong, S-J.
- Abstract
Background Thromboxane A2 receptor ( TBXA2R) gene polymorphism has been associated with atopy and asthma, but few studies have reported the effect of this gene polymorphism on asthma-related phenotype or responsiveness to leukotriene receptor antagonist (LTRA) in asthmatic children. This study investigated associations between asthma-related phenotypes and TBXA2R polymorphism, and also analysed whether the TBXA2R polymorphism has an effect on the efficacy of the LTRA, montelukast, in asthmatic children with exercise-induced bronchoconstriction (EIB). Methods Asthmatic children ( n=695) and control children ( n=159) were evaluated for asthma-related phenotypes including total IgE, pulmonary function test, and bronchial hyperresponsiveness to methacholine or exercise. Genotypes were detected by PCR-RFLP. In the montelukast study, exercise challenge was performed before and after an 8-week montelukast treatment. Results The TBXA2R polymorphism was not associated with asthma susceptibility and the clinical parameters of asthma. However, asthmatic children with combinations of the TBXA2R+795T>C and +924T>C risk alleles had significantly higher total IgE levels ( P=0.01), total eosinophil counts ( P<0.01) and lower forced expiratory volume in 1 s (FEV1) ( P=0.02) and forced expiratory rates at 25–75% of vital capacity ( P=0.02) than those carrying the common alleles. When compared with individuals with the common alleles, patients with the TBXA2R+924T>C TT homozygote and TBXA2R+795T>C hetero- or homozygote (CT or CC) had a 3.67-fold poor response to 8-week montelukast treatment with respect to maximum percent fall in FEV1 after exercise (odds ratio, 3.67; 95% confidence interval, 1.15–11.15). Conclusions A combined effect of TBXA2R+795T>C and +924T>C risk alleles may be linked to IgE production, eosinophilic inflammation, and severity of asthma. In addition, the TBXA2R+795T>C genotype may be a predictive marker of a clinical response to the LTRA in Korean asthmatic children with EIB.
- Subjects
GENETIC polymorphisms; LEUKOTRIENE antagonists; THROMBOXANES; ASTHMA; OBSTRUCTIVE lung diseases
- Publication
Clinical & Experimental Allergy, 2008, Vol 38, Issue 1, p51
- ISSN
0954-7894
- Publication type
Article
- DOI
10.1111/j.1365-2222.2007.02874.x