title: Inhaled corticosteroid treatment modulates ZNF432 gene variant's effect on bronchodilator response in asthmatics.
abstract: BACKGROUND
  Single nucleotide polymorphisms (SNPs) influence a patient's response to inhaled corticosteroids and β2-agonists, and the effect of treatment with inhaled corticosteroids is synergistic with the effect of β2-agonists. We hypothesized that use of inhaled corticosteroids could influence the effect of SNPs associated with a bronchodilator response.
  
  
  OBJECTIVE
  To assess whether, among subjects with asthma, the association of SNPs with bronchodilator response is different between those treated with inhaled corticosteroids versus those on placebo.
  
  
  METHODS
  A genome-wide association analysis was conducted by using 581 white subjects from the Childhood Asthma Management Program. By using data for 449,540 SNPs, we conducted a gene by environment analysis in PLINK with inhaled corticosteroid treatment as the environmental exposure and bronchodilator response as the outcome measure. We attempted to replicate the top 12 SNPs in the Leukotriene Modifier or Corticosteroid or Corticosteroid-Salmeterol Trial.
  
  
  RESULTS
  The combined P value for the Childhood Asthma Management Program and Leukotriene Modifier or Corticosteroid or Corticosteroid-Salmeterol Trial populations was 4.8 × 10(-8) for rs3752120, which is located in the zinc finger protein gene ZNF432 and has an unknown function.
  
  
  CONCLUSIONS
  Inhaled corticosteroids appear to modulate the association of bronchodilator response with variant(s) in the ZNF432 gene among adults and children with asthma.
authors.affiliation: Center for Child Health Care Studies, Department of Population Medicine, Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, Mass; Department of Pediatrics, Children's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass. Electronic address: ann.wu@childrens.harvard.edu.
authors.forename: Ann Chen
authors.initials: AC
authors.lastname: Wu
authors.affiliation: Harvard Medical School, Boston, Mass; Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, Mass; Center for Genomic Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Mass.
authors.forename: Blanca E
authors.initials: BE
authors.lastname: Himes
authors.affiliation: Harvard Medical School, Boston, Mass; Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, Mass; Center for Genomic Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Mass.
authors.forename: Jessica
authors.initials: J
authors.lastname: Lasky-Su
authors.affiliation: Harvard Medical School, Boston, Mass; Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, Mass; Center for Genomic Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Mass.
authors.forename: Augusto
authors.initials: A
authors.lastname: Litonjua
authors.affiliation: Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Peters
authors.affiliation: Nemours Children's Clinic, Centers for Clinical Pediatric Pharmacology and Pharmacogenetics, for the American Lung Association Asthma Clinical Research Centers, Jacksonville, Fla.
authors.forename: John
authors.initials: J
authors.lastname: Lima
authors.affiliation: Riken Center for Genomic Medicine, Kanagawa, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.affiliation: Riken Center for Genomic Medicine, Kanagawa, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Tamari
authors.affiliation: Laboratory of Molecular Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Harvard Medical School, Boston, Mass; Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, Mass; Center for Genomic Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Mass.
authors.forename: Weiliang
authors.initials: W
authors.lastname: Qiu
authors.affiliation: Harvard Medical School, Boston, Mass; Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, Mass; Center for Genomic Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Mass.
authors.forename: Scott T
authors.initials: ST
authors.lastname: Weiss
authors.affiliation: Harvard Medical School, Boston, Mass; Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, Mass; Center for Genomic Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Mass.
authors.forename: Kelan
authors.initials: K
authors.lastname: Tantisira
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics*; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D012097:Repressor Proteins / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: D000305:Adrenal Cortex Hormones; D001993:Bronchodilator Agents; D012097:Repressor Proteins; C588131:zinc finger protein 432, human
keywords: Asthma; ZNF432; bronchodilator response; inhaled corticosteroids; lung function; single nucleotide polymorphisms; zinc finger proteins