title: GENETIC INTERACTIONS BETWEEN ADRB2 AND PTGER4 ON RESPONSES TO SALMETEROL OR MONTELUKAST IN JAPANESE PATIENTS WITH MILD PERSISTENT ASTHMA.
abstract: Long-acting β2-agonists (LABA) and leukotriene receptor antagonists (LTRA) are two principal agents that can be added to inhaled corticosteroids (ICS) for patients with asthma that is not adequately controlled by ICS alone. In our previous study, the Gly16Arg genotype of the β2-adrenergic receptor (ADRB2) gene did not influence the differential bronchodilator effect of salmeterol versus montelukast as an add-on therapy to ICS within 16 weeks of follow-up (the J-Blossom study).
  
  
  
  We examined if genes encoding CYSLTR1, CYSLTR2, PTGER2 or PTGER4 could explain differential responses to salmeterol versus montelukast using the participants of the J-Blossom study. This study included 76 patients with mild-to-moderate asthma. The difference in peak expiratory flow (PEF) (ΔPEF, l/min) after 16 weeks of treatment with salmeterol (ΔPEFsal) versus montelukast (ΔPEFmon) was associated with the genotypes at each of 4 genes. In addition, multivariate analyses were used to identify a gene-gene interaction between ADRB2 gene and each of these 4 genes.
  
  
  
  Although none of 4 genes were associated with ΔPEFsal-ΔPEFmon in the univariate analyses, multivariate analysis showed that PTGER4 gene, interacting with ADRB2 Gly16Arg, was associated with ΔPEFsal-ΔPEFmon (p=0.0032).
  
  
  
  Our findings suggested that the interactions between two genetic loci at ADRB2 and PTGER4 is important in determining the differential response to salmeterol versus montelukast in patients with chronic adult asthma.
authors.affiliation: Department of Pulmonary Medicine, University of Tsukuba.
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Yamada
authors.forename: Hironori
authors.initials: H
authors.lastname: Masuko
authors.forename: Toshihide
authors.initials: T
authors.lastname: Inui
authors.forename: Jun
authors.initials: J
authors.lastname: Kanazawa
authors.forename: Yohei
authors.initials: Y
authors.lastname: Yatagai
authors.forename: Tohru
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Iijima
authors.forename: Satoshi
authors.initials: S
authors.lastname: Konno
authors.forename: Kaoruko
authors.initials: K
authors.lastname: Shimizu
authors.forename: Hironi
authors.initials: H
authors.lastname: Makita
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nishimura
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: Norihiro
authors.initials: N
authors.lastname: Kaneko
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hizawa
mesh_terms: D000085:Acetates / Q000627:therapeutic use*; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics*; D003521:Cyclopropanes; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011804:Quinolines / Q000627:therapeutic use*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000235:genetics*; D000068299:Salmeterol Xinafoate / Q000627:therapeutic use*; D013440:Sulfides
chemical_list: C553443:ADRB2 protein, human; D000085:Acetates; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; C545650:PTGER4 protein, human; D011804:Quinolines; D018343:Receptors, Adrenergic, beta-2; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013440:Sulfides; D000068299:Salmeterol Xinafoate; C093875:montelukast