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DNA methylation is associated with improvement in lung function on inhaled corticosteroids in pediatric asthmatics.

ABSTRACT: Asthma is the most common chronic disease in children. Inhaled corticosteroids (ICS) are the first-line treatment for asthma control, but up to one-third of children have a poor treatment response. The mechanism of ICS resistance is poorly understood, and the role of DNA methylation in ICS treatment response is not known. We examined the association between peripheral blood DNA methylation and ICS treatment response in 152 pediatric persistent asthmatics from the Childhood Asthma Management Program. Response to ICS was measured by the percentage change in forced expiratory volume in 1?s (FEV1) 8 weeks after treatment initiation. The top CpG sites with a nominal P value less than 0.001 were correlated with gene expression using Pearson's and partial correlations. In 152 participants, mean±SD age was 9.8±2.0?years and median change in FEV1 after ICS initiation was 4.6% (interquartile range: 10.4%). A total of 545 CpG sites were differentially methylated (nominal P<0.05), and seven CpG sites had a nominal P value less than 0.001. Relative hypermethylation of cg20434811, cg02822723, cg14066280, cg27254601, and cg23913400 and relative hypomethylation of cg24937126 and cg24711626 were associated with an increase in FEV1 on ICS treatment. One CpG site was associated with gene expression. Relative hypermethylation of cg27254601 was associated with both an increase in FEV1 and BOLA2 expression (?=0.25, P=0.02). We identified a novel association between BOLA2 methylation, gene expression, and ICS response as measured by lung function. Pharmacoepigenetics has the potential to detect treatment sensitivity in persistent childhood asthma.

SUBMITTER: Wang AL

PROVIDER: S-EPMC6399026 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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DNA methylation is associated with improvement in lung function on inhaled corticosteroids in pediatric asthmatics.

Wang Alberta L AL Qiu Weiliang W DeMeo Dawn L DL Raby Benjamin A BA Weiss Scott T ST Tantisira Kelan G KG

Pharmacogenetics and genomics 20190401 3

Asthma is the most common chronic disease in children. Inhaled corticosteroids (ICS) are the first-line treatment for asthma control, but up to one-third of children have a poor treatment response. The mechanism of ICS resistance is poorly understood, and the role of DNA methylation in ICS treatment response is not known. We examined the association between peripheral blood DNA methylation and ICS treatment response in 152 pediatric persistent asthmatics from the Childhood Asthma Management Prog ...[more]

PMID: 30640894

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Project description:Background: The first step in SARS-CoV-2 infection is binding of the virus to angiotensin converting enzyme 2 (ACE2) on the airway epithelium. Asthma affects over 300 million people world-wide, many of whom may encounter SARS-CoV-2. Epidemiologic data suggests that asthmatics who get infected may be at increased risk of more severe disease. Our objective was to assess whether maintenance inhaled corticosteroids (ICS), a major treatment for asthma, is associated with airway ACE2 expression in asthmatics. Methods: Large airway epithelium (LAE) of asthmatics treated with maintenance ICS (ICS+), asthmatics not treated with ICS (ICS-), and healthy controls (controls) was analyzed for expression of ACE2 and other coronavirus infection-related genes using microarrays. Results: AsResults: As a group, there was no difference in LAE ACE2 expression in all asthmatics vs controls. In contrast, subgroup analysis demonstrated that LAE ACE2 expression was higher in asthmatics ICS+ compared to ICS‾ and ACE2 expression was higher in male ICS+ compared to female ICS+ and ICS‾ of either sex. ACE2 expression did not correlate with serum IgE, absolute eosinophil level, or change in FEV1 in response to bronchodilators in either ICS- or ICS+. Conclusion: Airway ACE2 expression is increased in asthmatics on long-term treatment with ICS, an observation that should be taken into consideration when assessing the use of inhaled corticosteroids during the pandemic. a group, there was no difference in LAE ACE2 expression in all asthmatics vs controls. In contrast, subgroup analysis demonstrated that LAE ACE2 expression was higher in asthmatics ICS+ compared to ICS‾ and ACE2 expression was higher in male ICS+ compared to female ICS+ and ICS‾ of either sex. ACE2 expression did not correlate with serum IgE, absolute eosinophil level, or change in FEV1 in response to bronchodilators in either ICS- or ICS+. Conclusion: Airway ACE2 expression is increased in asthmatics on long-term treatment with ICS, an observation that should be taken into consideration when assessing the use of inhaled corticosteroids during the pandemic.

Dataset Information

DNA methylation is associated with improvement in lung function on inhaled corticosteroids in pediatric asthmatics.

Publications

DNA methylation is associated with improvement in lung function on inhaled corticosteroids in pediatric asthmatics.

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