title: An environmental epigenetic study of  ADRB2 5'-UTR methylation and childhood asthma severity.
abstract: BACKGROUND
  Beta-2 adrenergic receptor (ADRB2) is the primary target of both short- and long-acting beta-agonist asthma medications. ADRB2 5'-UTR methylation changes in blood have the potential to act as a surrogate biomarker of responsiveness to beta-agonist treatment and childhood asthma severity.
  
  
  OBJECTIVE
  To study the association between ADRB2 5'-UTR methylation, NO (2)  exposure and childhood asthma severity.
  
  
  METHODS
  We compared ADRB2 5'-UTR methylation levels in blood between 60 children with mild asthma and 122 children with severe asthma using methylation-specific PCR. We also investigated potential joint effects between NO (2)  exposure and ADRB2 5'-UTR methylation.
  
  
  RESULTS
  We found a significant association between intermediate (OR: 4.11, 95% CI: 1.58-10.73) and high levels (OR: 7.63, 95% CI: 3.02-19.26) of ADRB2 methylation and severe childhood asthma. In addition, we found a significant association between indoor exposure to NO (2) , an air pollutant and known asthmogen, and severe asthma among children exhibiting high ADRB2 methylation (OR: 4.59, 95% CI: 1.03-20.55) but no association among children exhibiting low levels of ADRB2 methylation (OR: 0.35, 95% CI: 0.01-14.13).
  
  
  CONCLUSIONS
  These findings support the potential use of ADRB2 5'-UTR methylation as a biomarker of both asthma severity and risk for NO (2) -associated asthma exacerbations in children, and present the first evidence of an epigenetic link between an important environmental exposure and childhood asthma severity.
authors.affiliation: Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT 06520, USA.
authors.forename: A
authors.initials: A
authors.lastname: Fu
authors.forename: B P
authors.initials: BP
authors.lastname: Leaderer
authors.forename: J F
authors.initials: JF
authors.lastname: Gent
authors.forename: D
authors.initials: D
authors.lastname: Leaderer
authors.forename: Y
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D020121:5' Untranslated Regions; D000293:Adolescent; D001249:Asthma / Q000209:etiology* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D018899:CpG Islands; D019175:DNA Methylation; D004781:Environmental Exposure; D044127:Epigenesis, Genetic; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D008297:Male; D009585:Nitrogen Dioxide; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012306:Risk; D012720:Severity of Illness Index
chemical_list: D020121:5' Untranslated Regions; D018343:Receptors, Adrenergic, beta-2; D009585:Nitrogen Dioxide