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Clin Exp Allergy. 2012 Nov;42(11):1575-81. doi: 10.1111/j.1365-2222.2012.04055.x. Epub 2012 Aug 3.

An environmental epigenetic study of ADRB2 5'-UTR methylation and childhood asthma severity.

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  • 1Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT 06520, USA.

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 AND CLINICAL RELEVANCE:

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.

© 2012 Blackwell Publishing Ltd.

PMID:
22862293
[PubMed - indexed for MEDLINE]
PMCID:
PMC3673701
Free PMC Article
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