title: Polymorphisms of the PTGDR and LTC4S influence responsiveness to leukotriene receptor antagonists in Korean children with asthma.
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.
authors.affiliation: Asan Institute for Life Sciences, University of Ulsan, Seoul, Korea.
authors.forename: Mi-Jin
authors.initials: MJ
authors.lastname: Kang
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Kwon
authors.forename: Byoung-Ju
authors.initials: BJ
authors.lastname: Kim
authors.forename: Jinho
authors.initials: J
authors.lastname: Yu
authors.forename: Won-Ah
authors.initials: WA
authors.lastname: Choi
authors.forename: Yee-Jin
authors.initials: YJ
authors.lastname: Shin
authors.forename: Soo-Jong
authors.initials: SJ
authors.lastname: Hong
mesh_terms: D000085:Acetates / Q000494:pharmacology / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000235:genetics*; D002648:Child; D003521:Cyclopropanes; D005080:Exercise Test; D005453:Fluorescence; D055106:Genome-Wide Association Study; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D007073:Immunoglobulin E / Q000097:blood; D007723:Korea; D020024:Leukotriene Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use; D011971:Receptors, Immunologic / Q000235:genetics*; D011982:Receptors, Prostaglandin / Q000235:genetics*; D013440:Sulfides
chemical_list: D000085:Acetates; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D013440:Sulfides; D007073:Immunoglobulin E; D005982:Glutathione Transferase; C041116:leukotriene-C4 synthase; C093875:montelukast; C036293:prostaglandin D2 receptor