DNA Methylomic Differences in Adults Asthmatics of Varying Severity and Exposure to Air Pollution

Rationale: DNA methylation plays a critical role in asthma development, but differences in DNA methylation associated with asthma severity, especially among adults, are less well-defined. Changes in DNA methylation are influenced by exposure to air pollution, which is a risk factor for asthma exacerbation and severity. Here, we examined how DNA methylomic patterns in adult asthmatics differ by asthma severity and exposure to different components of air pollution. Methods: Peripheral blood CD3+ T cells from adult asthmatics in Beijing, China were serially collected from 37 patients (130 samples total) and analyzed for global DNA methylation using the Illumina MethylationEPIC Array. Measurements and Main Results: Significant differences in DNA methylation were noted among subjects with different degrees of asthma severity, as measured by fraction of exhaled nitric oxide, forced expiratory volume, and asthma control test scores. Differences in DNA methylation were annotated to genes that were enriched in pathways related to asthma or T cell function, and included gene ontology categories related to cellular adhesion, developmental pathways, and calcium signaling. Notable genes that were differentially methylated based on asthma severity included RUNX3, several members of the HLA family, PDGFRA, CDH1, CAV1, and NOTCH4. Differences in DNA methylation also varied by exposure to ambient air pollution, with different components of pollution effecting methylation of different groups of genes. Conclusion: These findings demonstrate how adult asthmatics possess widespread differences in the DNA methylation that associated with varying asthma severity and how air pollution might contribute to more severe asthma via changes in DNA methylation. Blood samples were collected at baseline (0), 3 months (V3), 6 months (V6), 9 months (V9), and 12 months (V12) from 37 adults in Beijing, China with a clinical diagnosis of asthma. CD3+ T cells were isolated from blood samples using anti-CD3 magnetic particles and DNA was extracted from these cells using the QlAmp DNA Micro Kit before bisulfite conversion and analysis on the Illumina Infinium MethylationEPIC BeadChip array. Clinical data including lung function, fraction of exhaled nitric oxide, and asthma control test results were collected at the time of blood sample collection and changes in methylation were correlated with clinical parameters of asthma. Sample number indicates different subject IDs.