EWAS in COPD by biomass-burning smoke exposure identifies low levels of endothelin-1 by hypermethylation of EDN1
<p>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...
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2025
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| Resumo: | <p>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).</p> <p>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.</p> <p>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).</p> <p>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.</p> <p>DNA modifications not present in the sequence contribute to COPD in women exposed to biomass-burning smoke.</p> <p>In both rural and urban areas, using biomass (firewood) for cooking and heating homes is quite common. Unfortunately, the smoke produced from burning firewood contains substances harmful to the respiratory system.</p> <p>The primary population affected is women, leading some to develop lung disease. The aim of this study was to assess the changes that genetic material can exhibit and their impact on the production of proteins involved in the disease.</p> <p>We found a significant effect on genes that play roles in inflammation and detoxification processes in the body. Notably, our findings highlight the influence on the endothelin gene, which encodes a protein that regulates inflammatory responses and manages high blood pressure in the pulmonary arteries.</p> <p>These results will enable us to explore additional pathways that have not been previously analyzed to gain further insight into the disease.</p> |
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