Is the association between the severity of airflow limitation and DNA Methylation similar in blood and lung tissue in patients with COPD?
Background: Epigenetic Changes and DNA Methylation in COPD
Previous studies have reported epigenetic changes in lung tissue or blood of COPD patients but whether the relationship of methylation changes with the severity of airflow limitation is similar or different in both tissues is unknown.
Methods: Assessing DNA Methylation in Blood and Lung Tissue of COPD Patients
DNA was extracted from blood (n=269) and lung tissue (n=140) of COPD patients with different levels of airflow limitation (FEV1 % ref.). DNA methylation was assessed with the EPIC array (Illumina).
CpG-sites associated with FEV1 %ref. in blood and lung tissue, were determined using multivariate regression adjusted for age, sex, smoking status and packs/year.
Results: Opposite Associations of DNA Methylation with Airflow Limitation in COPD
Both in blood and lung tissue, 4,979 CpGs were associated with FEV1% ref. (FDR<0.05). Interestingly, 98% of these CpGs presented an opposite association with FEV1% ref. between the two tissues.
Annotated genes showing a negative association with FEV1% ref. in blood, but a positive association in lung tissue were enriched for ontologies related to actin organization, T cell differentiation, cell signaling and morphogenesis.
Conversely, annotated genes with a positive association to FEV1% ref. in blood (but negative in lung tissue) were enriched for cell junction assembly, cell-matrix adhesion and cell migration ontologies.
Conclusions: Differential Regulation of DNA Methylation in Blood and Lung Tissues in COPD
Blood and lung DNA share differentially methylated positions in relation to the severity of airflow limitation.
However most of them present an opposite direction of effect suggesting that both tissues are differentially regulated.
Authors
Sandra Casas Recasens, Nuria Mendoza, Nuria Olvera, Lidia Perea, Tamara Garcia, Oriol Sibila, Àlvar Agustí, Rosa Faner
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