title: The effects of a Gly16Arg ADRB2 polymorphism on responses to salmeterol or montelukast in Japanese patients with mild persistent asthma.
abstract: BACKGROUND
  Long-acting β2-agonists and leukotriene receptor antagonists are two principal agents that can be added to inhaled corticosteroids (ICS) for patients with asthma that is not adequately controlled by ICS alone. The Gly16Arg genotype of the β2-adrenergic receptor (ADRB2) gene may influence the bronchodilator effects of β2-agonists. We hypothesized that differential responses to long-acting β2-agonists or leukotriene receptor antagonists might be determined partly by the Gly16Arg polymorphism in Japanese asthma patients.
  
  
  METHODS
  This randomized, genotype-stratified, two-period crossover study included 80 patients with mild-to-moderate asthma (35 Arg/Arg and 45 Gly/Gly individuals). The primary study outcome was the difference in peak expiratory flow (ΔPEF) (ΔPEF, l/min) by genotype after 16 weeks of treatment with salmeterol (ΔPEFsal) or montelukast (ΔPEFmon). In addition, multivariate analyses were used to identify independent factors that were predictive of responses to each treatment.
  
  
  RESULTS
  The mean ΔPEFsal-ΔPEFmon was 19.3±46.6 among Arg/Arg individuals and 16.8±51.5 among Gly/Gly individuals, indicating that the Gly16Arg genotype did not influence the differential bronchodilator effect of the two agents. Multivariate analysis showed that higher peripheral eosinophil counts were associated with better response to salmeterol (P<0.05).
  
  
  CONCLUSIONS
  The Gly16Arg genotype did not influence the differential bronchodilator effect of salmeterol or montelukast as an add-on therapy to ICS within 16 weeks of follow-up. Higher peripheral eosinophil counts may be associated with better responses to salmeterol in combination with ICS.
authors.affiliation: aFirst Department of Medicine, Hokkaido University School of Medicine, Sapporo bDepartment of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba cDepartment of Respiratory Medicine, Showa University Fujigaoka Hospital, Tokyo dDepartment of Respiratory Medicine, Ibaraki Higashi National Hospital, Ibaraki eDepartment of Respiratory Medicine, Mito Medical Center, Mito fDepartment of Respiratory Medicine, Kobari General Hospital, Chiba gDepartment of Respiratory Medicine, Tsukuba Medical Center, Tsukuba hDepartment of Respiratory Medicine, Kameda Medical Center, Chiba iDepartment of Biostatistics, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Konno
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hizawa
authors.forename: Hironi
authors.initials: H
authors.lastname: Makita
authors.forename: Kaoruko
authors.initials: K
authors.lastname: Shimizu
authors.forename: Tohru
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Fumio
authors.initials: F
authors.lastname: Kokubu
authors.forename: Takefumi
authors.initials: T
authors.lastname: Saito
authors.forename: Takeo
authors.initials: T
authors.lastname: Endo
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ninomiya
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Iijima
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kaneko
authors.forename: Yoichi M
authors.initials: YM
authors.lastname: Ito
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nishimura
mesh_terms: D000085:Acetates / Q000008:administration & dosage*; D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001249:Asthma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D003521:Cyclopropanes; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011804:Quinolines / Q000008:administration & dosage*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D000068299:Salmeterol Xinafoate; D013440:Sulfides
chemical_list: C553443:ADRB2 protein, human; D000085:Acetates; D000305:Adrenal Cortex Hormones; D003521:Cyclopropanes; D011804:Quinolines; D018343:Receptors, Adrenergic, beta-2; D013440:Sulfides; D000068299:Salmeterol Xinafoate; C093875:montelukast; D000420:Albuterol