EWAS in COPD by biomass-burning smoke exposure identifies low levels of endothelin-1 by hypermethylation of EDN1

<h4>Background</h4>Exposure to smoke from biomass combustion is a significant environmental risk factor for chronic obstructive pulmonary disease (COPD). Through epigenome-wide association studies (EWAS), changes in DNA methylation levels associated with pathological conditions can be identified. We aimed to determine the methylation patterns in genes involved in the development of COPD resulting from exposure to biomass-burning smoke (COPD-BBS).<h4>Materials and methods</h4>EWAS was conducted on induced sputum samples from 45 women with stable COPD (COPD-BBS) exposure and 45 women exposed to BBS but without the disease (BBES). Proteins whose genes showed significant differences in methylation and were soluble in the induced sputum supernatant were quantified.<h4>Results</h4>205 CpG sites were found differentially hypomethylated, and 420 were hypermethylated. The top 50 show genes associated with lung remodeling (<i>FOXP1 p</i> = 0.002, <i>FMOD p</i> = 0.012, <i>EDN1 p</i> = 0.044), the immune system (<i>ALOX5 p</i> = 0.005, <i>IL19 p</i> = 0.047), mucus production (<i>MUC19 p</i> = 0.04), and xenobiotic metabolism (<i>GSTO2 p</i> = 0.02). Of the proteins evaluated, endothelin-1 was decreased in the reference group compared to patients (<i>p</i> = 0.00054).<h4>Conclusions</h4>Gene methylation changes are linked to lung remodeling, immune response, mucus production, and xenobiotic metabolism. Hypermethylation of the cg08450425 site (<i>EDN1</i>) is significant in women with COPD and associated with low endothelin-1 levels.