Korean J Pediatr.  2009 Jun;52(6):680-688. 10.3345/kjp.2009.52.6.680.

Association study of polymorphism in leukotriene C4 synthase and cysteinyl leukotriene receptor 1 genes with phenotype of asthma and clinical parameters in Korean children

Affiliations
  • 1Department of Pediatrics, Sungkyunkwan University School of Medicine, Korea.
  • 2Department of Pediatrics, University of Ulsan College of Medicine, Korea. sjhong@amc.seoul.kr
  • 3Asan Institute for Life Science, Korea.
  • 4Department of Pediatrics, University of Hallym College of Medicine, Korea.
  • 5Department of Pediatrics, Inje University, Korea.

Abstract

PURPOSE
Cysteinyl leukotrienes are important proinflammatory mediators in asthma. Recently, it was suggested that a promoter polymorphism in the genes encoding for leukotriene C4 synthase (LTC4S), a key enzyme in the leukotriene synthetic pathway, and cysteinyl leukotriene receptor 1 (CysLTR1) might be associated with aspirin-intolerant asthma. We investigated whether polymorphisms in LTC4S and CysLTR1 genes or their interactions were associated with the asthma phenotype, lung function, or bronchial hyperreactivity (BHR) in Korean children. METHODS: A total of 856 asthmatic children and 254 non-asthmatic controls were enrolled; a skin prick test, lung function test and bronchial provocation test were performed. Of those enrolled, 395 children underwent exercise challenge tests. The LTC4S A(-444)C and CysLTR1 T(+927)C were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: Of those enrolled, 699 children were classified as having atopic asthma and 277 children, as having exercise-induced asthma (EIA). LTC4S and CysLTR1 polymorphisms were not associated with atopic asthma, EIA, or asthma per se. Lung function and BHR were not significantly different between the wild type (AA or TT) and the variant (AC+CC or TC+CC) genotypes in asthmatics, atopic asthmatics, and EIA (+) asthmatics, while total eosinophil counts were higher in the variant type of LTC4S than in the wild type in atopic asthmatics. There were no associations between the gene-gene interactions of LTC4S and CysLTR1 genotypes and the asthma phenotypes. CONCLUSION: LTC4S A(-444)C and CysLTR1 T(+927)C polymorphisms and their gene-gene interactions are not associated with asthma phenotype, lung function, or BHR in Korean children.

Keyword

Exercised-induced asthma; Atopic asthma; Leukotriene C4 synthase; Cysteinyl leukotriene receptor 1; Polymorphism

MeSH Terms

Asthma
Asthma, Exercise-Induced
Bronchial Hyperreactivity
Bronchial Provocation Tests
Child
Eosinophils
Genotype
Humans
Leukotriene C4
Leukotrienes
Lung
Phenotype
Receptors, Leukotriene
Respiratory Function Tests
Skin
Leukotriene C4
Leukotrienes
Receptors, Leukotriene
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