Association of IL-13 polymorphisms with leukotriene receptor antagonist drug responsiveness in Korean children with exercise-induced bronchoconstriction.
BACKGROUND
IL-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/T polymorphism and the haplotype of IL-13 polymorphisms.


CONCLUSIONS
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.
Kang
Mi-Jin
MJ
Asan Institute for Life Sciences, University of Ulsan, Poongnap-dong Songpa-gu, Korea.
Lee
So-Yeon
SY
Kim
Hyo-Bin
HB
Yu
Jinho
J
Kim
Byoung-Ju
BJ
Choi
Won-Ah
WA
Jang
Seong-Ok
SO
Hong
Soo-Jong
SJ
D000085:Acetates / Q000627:therapeutic use*; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001250:Asthma, Exercise-Induced / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D016084:Bronchoconstriction / Q000187:drug effects / Q000235:genetics*; D002648:Child; D003521:Cyclopropanes; D004351:Drug Resistance / Q000235:genetics*; D005080:Exercise Test; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D018793:Interleukin-13 / Q000235:genetics*; D007723:Korea; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011804:Quinolines / Q000627:therapeutic use*; D013440:Sulfides
D000085:Acetates; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D018793:Interleukin-13; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D007073:Immunoglobulin E; C093875:montelukast