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Clinical & Experimental Allergy

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

Authors


Correspondence: Yong Zhu, Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT 06520, USA. E-mail: yong.zhu@yale.edu or Brian P. Leaderer, Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT 06520, USA. E-Mail: brian.leaderer@yale.edu

Summary

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.

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