Responsiveness to montelukast is associated with bronchial hyperresponsiveness and total immunoglobulin E but not polymorphisms in the leukotriene C4 synthase and cysteinyl leukotriene receptor 1 genes in Korean children with exercise-induced asthma (EIA).
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 FEV(1) 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.
Lee
S-Y
SY
Department of Pediatrics, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, Korea.
Kim
H-B
HB
Kim
J-H
JH
Kim
B-S
BS
Kang
M-J
MJ
Jang
S-O
SO
Seo
H-J
HJ
Hong
S-J
SJ
D000085:Acetates / Q000627:therapeutic use*; D001250:Asthma, Exercise-Induced / Q000188:drug therapy* / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy*; D002648:Child; D003521:Cyclopropanes; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007723:Korea; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011379:Prognosis; D011804:Quinolines / Q000627:therapeutic use*; D018077:Receptors, Leukotriene / Q000235:genetics*; D013440:Sulfides; D016896:Treatment Outcome
D000085:Acetates; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D011804:Quinolines; D018077:Receptors, Leukotriene; D013440:Sulfides; D007073:Immunoglobulin E; D005982:Glutathione Transferase; C041116:leukotriene-C4 synthase; C083169:leukotriene D4 receptor; C093875:montelukast