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An environmental epigenetic study of ADRB 2 5′‐ UTR methylation and childhood asthma severity
Author(s) -
Fu A.,
Leaderer B. P.,
Gent J. F.,
Leaderer D.,
Zhu Y.
Publication year - 2012
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2012.04055.x
Subject(s) - asthma , methylation , biomarker , medicine , epigenetics , dna methylation , clinical significance , immunology , oncology , bioinformatics , biology , genetics , gene expression , gene
Summary Background Beta‐2 adrenergic receptor ( ADRB 2) is the primary target of both short‐ and long‐acting beta‐agonist asthma medications. ADRB 2 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 ADRB 2 5′‐ UTR methylation, NO 2 exposure and childhood asthma severity. Methods We compared ADRB 2 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 ADRB 2 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 ADRB 2 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 ADRB 2 methylation ( OR : 4.59, 95% CI : 1.03–20.55) but no association among children exhibiting low levels of ADRB 2 methylation ( OR : 0.35, 95% CI : 0.01–14.13). Conclusions and Clinical Relevance These findings support the potential use of ADRB 2 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.