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Keywords:

  • Cysteinyl leukotriene;
  • Cysteinyl leukotriene receptor 1;
  • exercise-induced bronchoconstriction;
  • Leukotriene receptor antagonist;
  • LTC4S promoter;
  • Pharmacogenetics

Summary

Background As previous studies have shown that cysteinyl leukotrienes are important mediators in exercise-induced bronchoconstriction (EIB), and leukotriene receptor antagonists (LTRAs) such as montelukast have been shown to improve post-exercise bronchoconstrictor responses, we herein investigated whether clinical responsiveness to montelukast was associated with polymorphisms in the genes encoding leukotriene C4 synthase (LTC4S) and cysteinyl leukotriene receptor 1 (CysLTR1) and/or clinical parameters in Korean asthmatic children with EIB.

Methods The study population consisted of 100 asthmatic children with EIB. The individuals studied were given exercise challenge tests before and after receiving montelukast (5 mg/day) for 8 weeks. Responders were defined as children showing>10% post-treatment improvement in forced expiratory volume in 1 s (FEV1). The LTC4S A(−444)C and CysLTR1 T(+927)C polymorphisms were genotyped by PCR-restriction fragment length polymorphism analysis.

Results Of 100 enrolled children, 68 were classified as responders and 32 were classified as non-responders. No significant association was observed between montelukast responsiveness and LTC4S or CysLTR1 genotype, either alone or in combination. In contrast, montelukast-induced improvement in FEV1 after exercise was correlated with higher pre-treatment PC20 (methacholine) values (r=0.210, P=0.036) and lower total IgE levels (r=−0.216, P=0.031).

Conclusions The LTC4S A(−444)C and CysLTR1 T(+927)C genotypes do not appear to be useful for predicting clinical responsiveness to montelukast, whereas bronchial hyperresponsiveness and total IgE appear to predict the degree of montelukast responsiveness in Korean asthmatic children with EIB.