Dataset Information

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 ?2-agonists, and the effect of treatment with inhaled corticosteroids is synergistic with the effect of ?2-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.

SUBMITTER: Wu AC

PROVIDER: S-EPMC3943570 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Wu Ann Chen AC Himes Blanca E BE Lasky-Su Jessica J Litonjua Augusto A Peters Stephen P SP Lima John J Kubo Michiaki M Tamari Mayumi M Nakamura Yusuke Y Qiu Weiliang W Weiss Scott T ST Tantisira Kelan K

The Journal of allergy and clinical immunology 20131123 3

<h4>Background</h4>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.<h4>Objective</h4>To assess whether, among subjects with asthma, the association of SNPs with bronchodilator response is different bet ...[more]

PMID: 24280104

Similar Datasets

Project description:BackgroundThere is much debate surrounding the use of inhaled bronchodilators and corticosteroids for infants with bronchopulmonary dysplasia (BPD).ObjectiveThe objective of this systematic review was to identify strengths and knowledge gaps in the literature regarding inhaled therapies in BPD and guide future research to improve long-termoutcomes.MethodsThe databases of Academic Search Complete, CINAHL, PUBMED/MEDLINE, and Scopus were searched for studies that evaluated both acute and long-term clinical outcomes related to the delivery and therapeutic efficacy of inhaled beta-agonists, anticholinergics and corticosteroids in infants with developing and/or established BPD.ResultsOf 181 articles, 22 met inclusion criteria for review. Five evaluated beta-agonist therapies (n = 84, weighted gestational age (GA) of 27.1(26-30) weeks, weighted birth weight (BW) of 974(843-1310) grams, weighted post menstrual age (PMA) of 34.8(28-39) weeks, and weighted age of 53(15-86) days old at the time of evaluation). Fourteen evaluated inhaled corticosteroids (n = 2383, GA 26.2(26-29) weeks, weighted BW of 853(760-1114) grams, weighted PMA of 27.0(26-31) weeks, and weighted age of 6(0-45) days old at time of evaluation). Three evaluated combination therapies (n = 198, weighted GA of 27.8(27-29) weeks, weighted BW of 1057(898-1247) grams, weighted PMA of 30.7(29-45) weeks, and age 20(10-111) days old at time of evaluation).ConclusionWhether inhaled bronchodilators and inhaled corticosteroids improve long-term outcomes in BPD remains unclear. Literature regarding these therapies mostly addresses evolving BPD. There appears to be heterogeneity in treatment responses, and may be related to varying modes of administration. Further research is needed to evaluate inhaled therapies in infants with severe BPD. Such investigations should focus on appropriate definitions of disease and subject selection, timing of therapies, and new drugs, devices and delivery methods as compared to traditional methods across all modalities of respiratory support, in addition to the assessment of long-term outcomes of initial responders.

Project description:Evidence suggests that variation in the length of the poly-C repeat in the 3' untranslated region (3'UTR) of the ?2-adrenergic receptor gene (ADRB2) may contribute to interindividual variation in ?-agonist response. However, methodology in previous studies limited the assessment of the effect of sequence variation in the context of poly-C repeat length. The objectives of this study were to design a novel genotyping method to fully characterize sequence variation in the ADRB2 3'UTR poly-C repeat in asthma patients treated with inhaled corticosteroid and long-acting ?2-adrenergic agonist (ICS/LABA) combination therapy, and to analyze the effect of the poly-C repeat polymorphism on clinical response.In 2,250 asthma patients randomized to treatment with budesonide/formoterol or fluticasone/salmeterol in a six-month study (AstraZeneca study code: SD-039-0735), sequence diversity in the ADRB2 poly-C repeat region was determined using a novel sequencing-based genotyping method. The relationship between the poly-C repeat polymorphism and the incidence of severe asthma exacerbations, and changes in pulmonary function and asthma symptoms from baseline to the average during the treatment period, were analyzed.Poly-C repeat genotypes were assigned in 97% (2,192/2,250) of patients. Of the 13 different poly-C repeat alleles identified, six alleles occurred at a frequency of >5% in one or more population in this study. The repeat length of these six common alleles ranged from 10 to 14 nucleotides. Twelve poly-C repeat genotypes were observed at a frequency of >1%. No evidence of an association between poly-C repeat genotype and the incidence of severe asthma exacerbations was observed. Patients' pulmonary function measurements improved and asthma symptoms declined when treated with ICS/LABA combination therapy regardless of poly-C repeat genotype.The extensive sequence diversity present in the poly-C repeat region of the ADRB2 3'UTR did not predict therapeutic response to ICS/LABA therapy.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets