title: Circulating MicroRNAs: Association with Lung Function in Asthma.
abstract: BACKGROUND
  MicroRNAs are key transcriptional and network regulators previously associated with asthma susceptibility. However, their role in relation to asthma severity has not been delineated.
  
  
  OBJECTIVE
  We hypothesized that circulating microRNAs could serve as biomarkers of changes in lung function in asthma patients.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Circulating microRNAs reflect asthma biology and are associated with lung function differences in asthmatics. They may represent biomarkers of asthma severity.
authors.affiliation: Children's Hospital Informatics Program, Boston Children's Hospital and Harvard Medical School, Boston MA 02115, United States of America.
authors.forename: Alvin T
authors.initials: AT
authors.lastname: Kho
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, CO 80045, United States of America.
authors.forename: Sunita
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, United States of America.|Pulmonary and Critical Care Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02115, United States of America.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Davis
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, United States of America.
authors.forename: Joseph
authors.initials: J
authors.lastname: Spina
authors.affiliation: Oregon Health & Science University, Portland, OR 97239, United States of America.
authors.forename: Dagnie
authors.initials: D
authors.lastname: Howard
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, United States of America.
authors.forename: Kevin
authors.initials: K
authors.lastname: McEnroy
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, United States of America.
authors.forename: Kip
authors.initials: K
authors.lastname: Moore
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, United States of America.
authors.forename: Jody
authors.initials: J
authors.lastname: Sylvia
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, United States of America.
authors.forename: Weiliang
authors.initials: W
authors.lastname: Qiu
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, United States of America.|Partners Personalized Medicine, Partners HealthCare System, Boston, MA 02115, United States of America.
authors.forename: Scott T
authors.initials: ST
authors.lastname: Weiss
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, United States of America.|Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, United States of America.
authors.forename: Kelan G
authors.initials: KG
authors.lastname: Tantisira
mesh_terms: D001249:Asthma / Q000235:genetics / Q000503:physiopathology*; D002648:Child; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008168:Lung / Q000503:physiopathology*; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D035683:MicroRNAs