title: Dual-specificity phosphatase 1 as a pharmacogenetic modifier of inhaled steroid response among asthmatic patients.
abstract: BACKGROUND
  Inhaled corticosteroids (ICSs) are considered first-line treatment for persistent asthma, yet there is significant variability in treatment response. Dual-specificity phosphatase 1 (DUSP1) appears to mediate the anti-inflammatory action of corticosteroids.
  
  
  OBJECTIVE
  We sought to determine whether variants in the DUSP1 gene are associated with clinical response to ICS treatment.
  
  
  METHODS
  Study participants with asthma were drawn from the following multiethnic cohorts: the Genetics of Asthma in Latino Americans (GALA) study; the Study of African Americans, Asthma, Genes & Environments (SAGE); and the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE). We screened GALA study participants for genetic variants that modified the relationship between ICS use and bronchodilator response. We then replicated our findings in SAGE and SAPPHIRE participants. In a group of SAPPHIRE participants treated with ICSs for 6 weeks, we examined whether a DUSP1 polymorphism was associated with changes in FEV(1) and self-reported asthma control.
  
  
  RESULTS
  The DUSP1 polymorphisms rs881152 and rs34507926 localized to different haplotype blocks and appeared to significantly modify the relationship between ICS use and bronchodilator response among GALA study participants. This interaction was also seen for rs881152 among SAPPHIRE but not SAGE participants. Among the group of SAPPHIRE participants prospectively treated with ICSs for 6 weeks, rs881152 genotype was significantly associated with changes in self-reported asthma control but not FEV(1).
  
  
  CONCLUSIONS
  DUSP1 polymorphisms were associated with clinical response to ICS therapy and therefore might be useful in the future to identify asthmatic patients more likely to respond to this controller treatment.
authors.affiliation: Center for Health Services Research, Henry Ford Health System, Detroit, Mich; Wayne State University School of Medicine, Detroit, Mich 48202, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jin
authors.forename: Donglei
authors.initials: D
authors.lastname: Hu
authors.forename: Edward L
authors.initials: EL
authors.lastname: Peterson
authors.forename: Celeste
authors.initials: C
authors.lastname: Eng
authors.forename: Albert M
authors.initials: AM
authors.lastname: Levin
authors.forename: Karen
authors.initials: K
authors.lastname: Wells
authors.forename: Kenneth
authors.initials: K
authors.lastname: Beckman
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kumar
authors.forename: Max A
authors.initials: MA
authors.lastname: Seibold
authors.forename: Gloria
authors.initials: G
authors.lastname: Karungi
authors.forename: Amanda
authors.initials: A
authors.lastname: Zoratti
authors.forename: John
authors.initials: J
authors.lastname: Gaggin
authors.forename: Janis
authors.initials: J
authors.lastname: Campbell
authors.forename: Joshua
authors.initials: J
authors.lastname: Galanter
authors.forename: Rocío
authors.initials: R
authors.lastname: Chapela
authors.forename: José R
authors.initials: JR
authors.lastname: Rodríguez-Santana
authors.forename: H Geoffrey
authors.initials: HG
authors.lastname: Watson
authors.forename: Kelley
authors.initials: K
authors.lastname: Meade
authors.forename: Michael
authors.initials: M
authors.lastname: Lenoir
authors.forename: William
authors.initials: W
authors.lastname: Rodríguez-Cintrón
authors.forename: Pedro C
authors.initials: PC
authors.lastname: Avila
authors.forename: David E
authors.initials: DE
authors.lastname: Lanfear
authors.forename: Esteban G
authors.initials: EG
authors.lastname: Burchard
authors.forename: L Keoki
authors.initials: LK
authors.lastname: Williams
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D002648:Child; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D012129:Respiratory Function Tests; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1