title: The glucocorticoid receptor heterocomplex gene STIP1 is associated with improved lung function in asthmatic subjects treated with inhaled corticosteroids.
abstract: BACKGROUND
  Corticosteroids exert their anti-inflammatory action by binding and activating the intracellular glucocorticoid receptor heterocomplex.
  
  
  OBJECTIVE
  We sought to evaluate the genes HSPCB, HSPCA, STIP1, HSPA8, DNAJB1, PTGES3, FKBP5, and FKBP4 on corticosteroid response.
  
  
  METHODS
  White asthmatic subjects (n = 382) randomized to once-daily flunisolide or conventional inhaled corticosteroid therapy were genotyped. Outcome measures were baseline FEV1, percent predicted FEV1, and percent change in FEV1 after corticosteroid treatment. Multivariable analyses adjusted for age, sex, and height were performed, fitting the most appropriate genetic model based on the quantitative mean derived from ANOVA models to determine whether there was an independent effect of polymorphisms on change in FEV1 independent of baseline level.
  
  
  RESULTS
  Positive recessive model correlations for STIP1 single nucleotide polymorphisms were observed for baseline FEV1 (rs4980524, P = .009; rs6591838, P = .0045; rs2236647, P = .002; and rs2236648; P = .013), baseline percent predicted FEV1 (rs4980524, P = .002; rs6591838, P = .017; rs2236647, P = .003; and rs2236648, P = .008), and percent change in FEV1 at 4 weeks (rs4980524, P = .044; rs6591838, P = .016; and rs2236647, P = .01) and 8 weeks (rs4980524, P = .044; rs6591838, P = .016; and rs2236647; P = .01) or therapy. Haplotypic associations were observed for baseline FEV1 and percent change in FEV1 at 4 weeks of therapy (P = .05 and P = .01, respectively). Significant trends toward association were observed for baseline percent predicted FEV1 and percent change in FEV1 at 8 weeks of therapy. Positive correlations between haplotypes and percent change in FEV1 were also observed.
  
  
  CONCLUSIONS
  STIP1 genetic variations might play a role in regulating corticosteroid response in asthmatic subjects with reduced lung function. Replication in a second asthmatic population is required to confirm these observations.
authors.affiliation: Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. ghawkins@wfubmc.edu
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Hawkins
authors.forename: Ross
authors.initials: R
authors.lastname: Lazarus
authors.forename: Richard S
authors.initials: RS
authors.lastname: Smith
authors.forename: Kelan G
authors.initials: KG
authors.lastname: Tantisira
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Meyers
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Peters
authors.forename: Scott T
authors.initials: ST
authors.lastname: Weiss
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Bleecker
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D005446:Fluocinolone Acetonide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005541:Forced Expiratory Volume / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015810:Linkage Disequilibrium; D008168:Lung / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016032:Randomized Controlled Trials as Topic; D011965:Receptors, Glucocorticoid / Q000378:metabolism
chemical_list: D018927:Anti-Asthmatic Agents; D006360:Heat-Shock Proteins; D011965:Receptors, Glucocorticoid; C079373:STIP1 protein, human; D005446:Fluocinolone Acetonide; C007734:flunisolide