PURPOSE OF THE STUDY.
The B2-adrenergic receptor (B2AR) is the major target of β-agonist bronchodilators. The gene encoding the B2AR (ADRB2) has been mapped to chromosome 5q31-33, a region identified as a susceptibility locus for asthma or atopy. Epigenetic changes are heritable changes in gene expression, not encoded by DNA sequence changes (eg, methylation of cytosine-phosphate guanine [CpG] islands within regulatory regions of DNA). A variably methylated CpG island overlaps ADRB2. The purpose of this study was to determine the effects of methylation on asthma symptoms, morbidity, and lung function.
This study was nested within the SICAS (School Inner-City Asthma Study) and involved children who had a physician’s diagnosis of asthma within the past 12 months.
DNA was extracted from saliva- and blood-derived samples. CpG sites were selected from the ADRB2 CpG island promoter region. DNA methylation assays were performed by staff blinded to the study. Methylation profiles for each locus represent a combination of saliva and blood sources. Caregivers completed questionnaires about asthma symptoms and rescue medication use within the past 4 weeks, as well as unscheduled health care visits and school absences related to asthma in the past 12 months. Subjects underwent prebronchodilator and postbronchodilator spirometry.
After adjusting for age, race, gender, preterm birth, family history of asthma, diagnosis of eczema, and sample source, percent methylation of the ADRB2 promoter showed a strong inverse association with dyspnea (odds ratio: 0.2; P = .002). There was no evidence of allele-specific differences in methylation.
This study is the first showing increased methylation at the ADRB2 gene being inversely associated with dyspnea, contributing to an improved asthma phenotype.
Typically, DNA CpG hypermethylation leads to decreased expression of the gene product. Data are inconsistent regarding the relationship between B2AR density in the airways and severity of asthma. This study showed that methylation can play a role in asthma phenotypes. More polymorphisms will need to be studied before concluding that methylation is independent of genotype.
- Copyright © 2014 by the American Academy of Pediatrics