In patients with chronic obstructive pulmonary disease (COPD), lung methylation profiles differ according to the severity of airflow limitation and some epigenetic changes translate into specific gene expression changes in the lung, according to study results published in the American Journal of Respiratory and Critical Care Medicine.1

Although tobacco smoking is the main risk factor for COPD, it does not develop in all smokers.1 Data demonstrate differential methylation patterns in relation to smoking and COPD, but are lacking on their relationship with severity of airflow limitations in lung tissue.2-4 Thus, researchers evaluated the relationships between the following: lung methylation changes, severity of airflow limitation, and active tobacco smoking exposure; and lung methylation and transcriptomic changes in the same individual.1 Lung tissue was obtained from individuals undergoing thoracic surgery and were categorized as never smokers with normal spirometry (n=26), current smokers with normal spirometry (n=11), former smokers with COPD (n=124), or current smokers with COPD (n=28).

Compared with never smokers, patients classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) 3-4 (moderately severe to severe) and GOLD 1-2 (mild to moderate) only share 10% of differentially methylated positions (DMPs), which implies that genes and biological processes that are deregulated in patients classified as GOLD 3-4 are different than those observed in patients classified as GOLD 1-2. Specifically, in patients classified as GOLD 1-2, DMPs relate to regulation of proteolysis, whereas in GOLD 3-4 they relate to regulation of protein phosphorylation, apoptosis, and immune response.

The researchers also found a larger number of smoking-associated DMPs in former smokers classified as GOLD 1-2 than in those classified as GOLD 3-4, even though both groups had similar cumulative smoking exposure and time since quitting.


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“The novel findings of this study are that in patients with COPD: 1) the lung methylome is related [to] the severity of airflow limitation; and 2) DMPs are related to mRNA levels measured in the same individuals,” the study authors explained.1

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

References

1. Casas-Recasens S, Noell G, Mendoza N, et al. Lung DNA methylation in COPD: relationship with smoking status and airflow limitation severity. Am J Respir Crit Care Med. Published online August 21, 2020. doi:10.1164/rccm.201912-2420LE

2. Joehanes R, Just AC, Marioni RE, et al. Epigenetic signatures of cigarette smoking. Circ Cardiovasc Genet. 2016;9:436-447.

3. Sundar IK, Yin Q, Baier BS, et al. DNA methylation profiling in peripheral lung tissues of smokers and patients with COPD. Clin Epigenetics. 2017;9:38.

4. Morrow JD, Cho MH, Hersh CP, et al. DNA methylation profiling in human lung tissue identifies genes associated with COPD. Epigenetics. 2016;11(10):730-739.