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Polymorphisms of the PTGDR and LTC4S influence responsiveness to leukotriene receptor antagonists in Korean children with asthma.

Authors
 Mi-Jin Kang ; Ji-Won Kwon ; Soo-Jong Hong ; Yee-Jin Shin ; Won-Ah Choi ; Jinho Yu ; Byoung-Ju Kim 
Citation
 Journal of Human Genetics, Vol.56(4) : 284~289, 2011 
Journal Title
 Journal of Human Genetics 
ISSN
 1434-5161 
Issue Date
2011
Abstract
Activation of the prostaglandin D2 receptor (PTGDR) may contribute to pulmonary vasodilation, bronchoconstriction, recruitment of eosinophils, basophils and T-lymphocytes, and enhanced synthesis of leukotriene C4. We investigated whether polymorphisms of the leukotriene C4 synthase (LTC4S) -444A/C and PTGDR -441T/C were associated with clinical phenotypes and responsiveness to leukotriene receptor antagonist (LTRA) in Korean asthmatic children. We enrolled 270 normal and 870 asthmatic children. We prescribed montelukast (5 mg per day) to 100 of asthmatic children, and analyzed the responsiveness to LTRA by exercise challenge tests. Polymorphisms were genotyped by PCR-restriction fragment length polymorphism. As the number of minor alleles of the PTGDR -441T/C and LTC4S -444A/C polymorphisms increased, the log total eosinophil counts increased in atopic asthmatic children (P-value=0.03). We found a significant association between responsiveness to montelukast and the PTGDR polymorphism (P-value=0.038). However, the LTC4S -444A/C and PTGDR -441T/C were not associated with the susceptibility for asthma (LTC4S, AA versus AC+CC, adjusted odds ratio of 0.98 (95% confidence interval, 0.73-1.31); PTGDR, TT versus TC+CC, adjusted odds ratio of 0.90 (95% confidence interval, 0.68-1.19)) or clinical phenotypes (P-value>0.05). The effects of the PTGDR and LTC4S polymorphisms on the enhancement of eosinophil counts were additive in the Korean children with asthma. In addition, the PTGDR polymorphism seems to be associated with the responsiveness to LTRA. Therefore, therapies that target the PTGDR may be useful for modulating the responsiveness to LTRA.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/93015
DOI
10.1038/jhg.2011.3
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Psychiatry
Yonsei Authors
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Link
 http://www.nature.com/jhg/journal/v56/n4/full/jhg20113a.html
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