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

Ann Chen Wu, Blanca E. Himes, Jessica Lasky-Su, Augusto Litonjua, Stephen P. Peters, John Lima, Michiaki Kubo, Mayumi Tamari, Yusuke Nakamura, Weiliang Qiu, Scott T. Weiss, Kelan Tantisira

Research output: Contribution to journalArticle

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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.

Original languageEnglish
JournalJournal of Allergy and Clinical Immunology
Volume133
Issue number3
DOIs
Publication statusPublished - 01-01-2014

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Bronchodilator Agents
Adrenal Cortex Hormones
Genes
Single Nucleotide Polymorphism
Asthma
Therapeutics
Leukotrienes
Genome-Wide Association Study
Zinc Fingers
Environmental Exposure
Placebos
Outcome Assessment (Health Care)

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Wu, Ann Chen ; Himes, Blanca E. ; Lasky-Su, Jessica ; Litonjua, Augusto ; Peters, Stephen P. ; Lima, John ; Kubo, Michiaki ; Tamari, Mayumi ; Nakamura, Yusuke ; Qiu, Weiliang ; Weiss, Scott T. ; Tantisira, Kelan. / Inhaled corticosteroid treatment modulates ZNF432 gene variant's effect on bronchodilator response in asthmatics. In: Journal of Allergy and Clinical Immunology. 2014 ; Vol. 133, No. 3.
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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.",
author = "Wu, {Ann Chen} and Himes, {Blanca E.} and Jessica Lasky-Su and Augusto Litonjua and Peters, {Stephen P.} and John Lima and Michiaki Kubo and Mayumi Tamari and Yusuke Nakamura and Weiliang Qiu and Weiss, {Scott T.} and Kelan Tantisira",
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Wu, AC, Himes, BE, Lasky-Su, J, Litonjua, A, Peters, SP, Lima, J, Kubo, M, Tamari, M, Nakamura, Y, Qiu, W, Weiss, ST & Tantisira, K 2014, 'Inhaled corticosteroid treatment modulates ZNF432 gene variant's effect on bronchodilator response in asthmatics', Journal of Allergy and Clinical Immunology, vol. 133, no. 3. https://doi.org/10.1016/j.jaci.2013.09.037

Inhaled corticosteroid treatment modulates ZNF432 gene variant's effect on bronchodilator response in asthmatics. / Wu, Ann Chen; Himes, Blanca E.; Lasky-Su, Jessica; Litonjua, Augusto; Peters, Stephen P.; Lima, John; Kubo, Michiaki; Tamari, Mayumi; Nakamura, Yusuke; Qiu, Weiliang; Weiss, Scott T.; Tantisira, Kelan.

In: Journal of Allergy and Clinical Immunology, Vol. 133, No. 3, 01.01.2014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Inhaled corticosteroid treatment modulates ZNF432 gene variant's effect on bronchodilator response in asthmatics

AU - Wu, Ann Chen

AU - Himes, Blanca E.

AU - Lasky-Su, Jessica

AU - Litonjua, Augusto

AU - Peters, Stephen P.

AU - Lima, John

AU - Kubo, Michiaki

AU - Tamari, Mayumi

AU - Nakamura, Yusuke

AU - Qiu, Weiliang

AU - Weiss, Scott T.

AU - Tantisira, Kelan

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

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