Association of IL-13 polymorphisms with leukotriene receptor antagonist drug responsiveness in Korean children with exercise-induced bronchoconstriction

Background I L-13 is a pivotal cytokine in allergic inflammation and bronchial hyperresponsiveness, and is known to influence leukotriene levels. Objective We investigated whether IL-13 polymorphisms may be associated with clinical phenotypes and drug responsiveness to the leukotriene receptor antagonist (LTRA) in Korean asthmatic children with exercise-induced bronchoconstriction (EIB). Methods We enrolled 242 normal controls and 374 patients with asthma. Of the asthmatic patients, 100 performed exercise challenge tests before and after receiving montelukast (5 mg/day) for 8 weeks and included 80 subjects in drug responsiveness analysis. We assessed IL-13 polymorphisms (- 1512A/C, - 1112C/T, +2044G/A) through PCR-restriction fragment length polymorphism analysis. Results Significantly higher total IgE levels and maximum percent fall in forced expiratory volume in 1 s (FEV1) (%) after exercise challenge test were found in asthmatic patients carrying one or two copies of the IL-13 +2044A versus those homozygous for + 2044G (P= 0.011 and 0.040, respectively). We further noted a correlation of total IgE with maximum percent fall in FEV1 (%)in asthmatic patients, as well as a reverse correlation with improvement of maximum percent fall in FEV1 (%) after exercise challenge tests. Finally, we observed a significant association between responsiveness to montelukast and IL-13 - 1112C/Tpolymorphism and the haplotype of IL-13 polymorphisms. Conclusion The IL-13 +2044G/A polymorphism may be associated with atopy and EIB severity in Korean children with EIB, and thus could potentially be considered as a disease-modifying gene. Moreover, the IL-13 - 1112C/T polymorphism and the haplotype of IL-13 polymorphisms seem to be associated with LTRA drug responsiveness, and thus might prove useful as a target for modulation of LTRA drug responsiveness. Pharmacogenetics and Genomics 18:551-558 (c) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.