title: GLCCI1 variant accelerates pulmonary function decline in patients with asthma receiving inhaled corticosteroids.
abstract: BACKGROUND
  In steroid-naive patients with asthma, several gene variants are associated with a short-term response to inhaled corticosteroid (ICS) treatment; this has mostly been observed in Caucasians. However, not many studies have been conducted for other ethnicities. Here, we aimed to determine the relationship between the annual decline in forced expiratory flow volume in one second (FEV1 ) and the variant of the glucocorticoid-induced transcript 1 gene (GLCCI1) in Japanese patients with asthma receiving long-term ICS treatment, taking into account the effect of high serum periostin levels, a known association factor of pulmonary function decline and a marker of refractory eosinophilic/Th2 inflammation.
  
  
  METHODS
  In this study, 224 patients with asthma receiving ICS treatment for at least 4 years were enrolled. The effects of single-nucleotide polymorphisms (SNPs) in GLCCI1, stress-induced phosphoprotein 1 (STIP1), and T gene on the decline in FEV1 of 30 ml/year or greater were determined.
  
  
  RESULTS
  Besides the known contributing factors, that is, the most intensive treatment step, ex-smoking, and high serum periostin levels (≥95 ng/ml), the GG genotype of GLCCI1 rs37973, and not other SNPs, was independently associated with a decline in FEV1 of 30 ml/year or greater. When patients were stratified according to their serum periostin levels, the GG genotype of rs37973 was significantly associated with blood eosinophilia (≥250/μl) in the high serum periostin group.
  
  
  CONCLUSIONS
  A GLCCI1 variant is a risk factor of pulmonary function decline in Japanese patients with asthma receiving long-term ICS treatment. Thus, GLCCI1 may be associated with response to ICS across ethnicities.
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Izuhara
authors.forename: H
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Y
authors.initials: Y
authors.lastname: Kanemitsu
authors.forename: K
authors.initials: K
authors.lastname: Izuhara
authors.forename: Y
authors.initials: Y
authors.lastname: Tohda
authors.forename: T
authors.initials: T
authors.lastname: Horiguchi
authors.forename: H
authors.initials: H
authors.lastname: Kita
authors.forename: K
authors.initials: K
authors.lastname: Kuwabara
authors.forename: K
authors.initials: K
authors.lastname: Tomii
authors.forename: K
authors.initials: K
authors.lastname: Otsuka
authors.forename: M
authors.initials: M
authors.lastname: Fujimura
authors.forename: N
authors.initials: N
authors.lastname: Ohkura
authors.forename: K
authors.initials: K
authors.lastname: Tomita
authors.forename: A
authors.initials: A
authors.lastname: Yokoyama
authors.forename: H
authors.initials: H
authors.lastname: Ohnishi
authors.forename: Y
authors.initials: Y
authors.lastname: Nakano
authors.forename: T
authors.initials: T
authors.lastname: Oguma
authors.forename: S
authors.initials: S
authors.lastname: Hozawa
authors.forename: T
authors.initials: T
authors.lastname: Nagasaki
authors.forename: I
authors.initials: I
authors.lastname: Ito
authors.forename: T
authors.initials: T
authors.lastname: Oguma
authors.forename: H
authors.initials: H
authors.lastname: Inoue
authors.forename: T
authors.initials: T
authors.lastname: Tajiri
authors.forename: T
authors.initials: T
authors.lastname: Iwata
authors.forename: J
authors.initials: J
authors.lastname: Ono
authors.forename: S
authors.initials: S
authors.lastname: Ohta
authors.forename: M
authors.initials: M
authors.lastname: Tamari
authors.forename: T
authors.initials: T
authors.lastname: Hirota
authors.forename: T
authors.initials: T
authors.lastname: Yokoyama
authors.forename: A
authors.initials: A
authors.lastname: Niimi
authors.forename: M
authors.initials: M
authors.lastname: Mishima
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use; D000368:Aged; D001249:Asthma / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology*; D015815:Cell Adhesion Molecules / Q000097:blood; D004804:Eosinophils / Q000276:immunology; D005260:Female; D005541:Forced Expiratory Volume; D056726:Genetic Association Studies; D014644:Genetic Variation; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D012129:Respiratory Function Tests; D012307:Risk Factors
chemical_list: D000305:Adrenal Cortex Hormones; D015815:Cell Adhesion Molecules; C561807:GLCCI1 protein, human; D006360:Heat-Shock Proteins; C512835:POSTN protein, human; D011965:Receptors, Glucocorticoid; C079373:STIP1 protein, human
keywords: GLCCI1 variant; asthma; inhaled corticosteroid treatment; periostin; pulmonary function decline