Dataset Information

Circulating MicroRNAs: Association with Lung Function in Asthma.

ABSTRACT: MicroRNAs are key transcriptional and network regulators previously associated with asthma susceptibility. However, their role in relation to asthma severity has not been delineated.We hypothesized that circulating microRNAs could serve as biomarkers of changes in lung function in asthma patients.We isolated microRNAs from serum samples obtained at randomization for 160 participants of the Childhood Asthma Management Program. Using a TaqMan microRNA array containing 754 microRNA primers, we tested for the presence of known asthma microRNAs, and assessed the association of the individual microRNAs with lung function as measured by FEV1/FVC, FEV1% and FVC%. We further tested the subset of FEV1/FVC microRNAs for sex-specific and lung developmental associations.Of the 108 well-detected circulating microRNAs, 74 (68.5%) had previously been linked to asthma susceptibility. We found 22 (20.3%), 4 (3.7%) and 8 (7.4%) microRNAs to be associated with FEV1/FVC, FEV1% and FVC%, respectively. 8 (of 22) FEV1/FVC, 3 (of 4) FEV1% and 1 (of 8) FVC% microRNAs had functionally validated target genes that have been linked via genome wide association studies to asthma and FEV1 change. Among the 22 FEV1/FVC microRNAs, 9 (40.9%) remain associated with FEV1/FVC in boys alone in a sex-stratified analysis (compared with 3 FEV1/FVC microRNAs in girls alone), 7 (31.8%) were associated with fetal lung development, and 3 (13.6%) in both. Ontology analyses revealed enrichment for pathways integral to asthma, including PPAR signaling, G-protein coupled signaling, actin and myosin binding, and respiratory system development.Circulating microRNAs reflect asthma biology and are associated with lung function differences in asthmatics. They may represent biomarkers of asthma severity.

SUBMITTER: Kho AT

PROVIDER: S-EPMC4928864 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Circulating MicroRNAs: Association with Lung Function in Asthma.

Kho Alvin T AT Sharma Sunita S Davis Joshua S JS Spina Joseph J Howard Dagnie D McEnroy Kevin K Moore Kip K Sylvia Jody J Qiu Weiliang W Weiss Scott T ST Tantisira Kelan G KG

PloS one 20160630 6

<h4>Background</h4>MicroRNAs are key transcriptional and network regulators previously associated with asthma susceptibility. However, their role in relation to asthma severity has not been delineated.<h4>Objective</h4>We hypothesized that circulating microRNAs could serve as biomarkers of changes in lung function in asthma patients.<h4>Methods</h4>We isolated microRNAs from serum samples obtained at randomization for 160 participants of the Childhood Asthma Management Program. Using a TaqMan mi ...[more]

PMID: 27362794

Similar Datasets

Project description:RationaleBronchodilator response (BDR) is a measure of improvement in airway smooth muscle tone, inhibition of liquid accumulation and mucus section into the lumen in response to short-acting beta-2 agonists that varies among asthmatic patients. MicroRNAs (miRNAs) are well-known post-translational regulators. Identifying miRNAs associated with BDR could lead to a better understanding of the underlying complex pathophysiology.ObjectiveThe purpose of this study is to identify circulating miRNAs associated with bronchodilator response in asthma and decipher possible mechanism of bronchodilator response variation.MethodsWe used available small RNA sequencing on blood serum from 1,134 asthmatic children aged 6 to 14 years who participated in the Genetics of Asthma in Costa Rica Study (GACRS). We filtered the participants into high and low bronchodilator response (BDR) quartiles and used DeSeq2 to identify miRNAs with differential expression (DE) in high (N= 277) vs low (N= 278) BDR group. Replication was carried out in the Leukotriene modifier Or Corticosteroids or Corticosteroid-Salmeterol trial (LOCCS), an adult asthma cohort. The putative target genes of DE miRNAs were identified, and pathway enrichment analysis was performed.ResultsWe identified 10 down-regulated miRNAs having odds ratios (OR) between 0.37 and 0.76 for a doubling of miRNA counts and one up-regulated miRNA (OR=2.26) between high and low BDR group. These were assessed for replication in the LOCCS cohort, where two miRNAs (miR-200b-3p and miR-1246) were associated. Further, functional annotation of 11 DE miRNAs were performed as well as of two replicated miRs. Target genes of these miRs were enriched in regulation of cholesterol biosynthesis by SREBPs, ESR-mediated signaling, G1/S transition, RHO GTPase cycle, and signaling by TGFB family pathways.ConclusionMiRNAs miR-1246 and miR-200b-3p are associated with both childhood and adult asthma BDR. Our findings add to the growing body of evidence that miRNAs play a significant role in the difference of asthma treatment response among patients as it points to genomic regulatory machinery underlying difference in bronchodilator response among patients.Trial registrationLOCCS cohort [ClinicalTrials.gov number: NCT00156819], GACRS cohort [ClinicalTrials.gov number: NCT00021840].

Dataset Information

Circulating MicroRNAs: Association with Lung Function in Asthma.

Publications

Circulating MicroRNAs: Association with Lung Function in Asthma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets