title: TBXA2R gene polymorphism and responsiveness to leukotriene receptor antagonist in children with asthma.
abstract: BACKGROUND
  Thromboxane A2 receptor (TBXA2R) gene polymorphism has been associated with atopy and asthma, but few studies have reported the effect of this gene polymorphism on asthma-related phenotype or responsiveness to leukotriene receptor antagonist (LTRA) in asthmatic children. This study investigated associations between asthma-related phenotypes and TBXA2R polymorphism, and also analysed whether the TBXA2R polymorphism has an effect on the efficacy of the LTRA, montelukast, in asthmatic children with exercise-induced bronchoconstriction (EIB).
  
  
  METHODS
  Asthmatic children (n=695) and control children (n=159) were evaluated for asthma-related phenotypes including total IgE, pulmonary function test, and bronchial hyperresponsiveness to methacholine or exercise. Genotypes were detected by PCR-RFLP. In the montelukast study, exercise challenge was performed before and after an 8-week montelukast treatment.
  
  
  RESULTS
  The TBXA2R polymorphism was not associated with asthma susceptibility and the clinical parameters of asthma. However, asthmatic children with combinations of the TBXA2R+795T>C and +924T>C risk alleles had significantly higher total IgE levels (P=0.01), total eosinophil counts (P<0.01) and lower forced expiratory volume in 1 s (FEV(1)) (P=0.02) and forced expiratory rates at 25-75% of vital capacity (P=0.02) than those carrying the common alleles. When compared with individuals with the common alleles, patients with the TBXA2R+924T>C TT homozygote and TBXA2R+795T>C hetero- or homozygote (CT or CC) had a 3.67-fold poor response to 8-week montelukast treatment with respect to maximum percent fall in FEV(1) after exercise (odds ratio, 3.67; 95% confidence interval, 1.15-11.15).
  
  
  CONCLUSIONS
  A combined effect of TBXA2R+795T>C and +924T>C risk alleles may be linked to IgE production, eosinophilic inflammation, and severity of asthma. In addition, the TBXA2R+795T>C genotype may be a predictive marker of a clinical response to the LTRA in Korean asthmatic children with EIB.
authors.affiliation: Department of Pediatrics, Ulsan University Hospital, Ulsan, Korea.
authors.forename: J-H
authors.initials: JH
authors.lastname: Kim
authors.forename: S-Y
authors.initials: SY
authors.lastname: Lee
authors.forename: H-B
authors.initials: HB
authors.lastname: Kim
authors.forename: H-S
authors.initials: HS
authors.lastname: Jin
authors.forename: J-H
authors.initials: JH
authors.lastname: Yu
authors.forename: B-J
authors.initials: BJ
authors.lastname: Kim
authors.forename: B-S
authors.initials: BS
authors.lastname: Kim
authors.forename: M-J
authors.initials: MJ
authors.lastname: Kang
authors.forename: S-O
authors.initials: SO
authors.lastname: Jang
authors.forename: S-J
authors.initials: SJ
authors.lastname: Hong
mesh_terms: D001249:Asthma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D015444:Exercise / Q000502:physiology; D005260:Female; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D008297:Male; D016210:Methacholine Chloride / Q000627:therapeutic use*; D011110:Polymorphism, Genetic / Q000235:genetics*; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D020024:Leukotriene Antagonists; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D016210:Methacholine Chloride; D007073:Immunoglobulin E