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J Allergy Clin Immunol. 2014 Mar;133(3):723-8.e3. doi: 10.1016/j.jaci.2013.09.037. Epub 2013 Nov 23.

Inhaled corticosteroid treatment modulates ZNF432 gene variant's effect on bronchodilator response in asthmatics.

Author information

1
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.
2
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.
3
Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC.
4
Nemours Children's Clinic, Centers for Clinical Pediatric Pharmacology and Pharmacogenetics, for the American Lung Association Asthma Clinical Research Centers, Jacksonville, Fla.
5
Riken Center for Genomic Medicine, Kanagawa, Japan.
6
Laboratory of Molecular Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

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.

KEYWORDS:

Asthma; ZNF432; bronchodilator response; inhaled corticosteroids; lung function; single nucleotide polymorphisms; zinc finger proteins

PMID:
24280104
PMCID:
PMC3943570
DOI:
10.1016/j.jaci.2013.09.037
[Indexed for MEDLINE]
Free PMC Article
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