Systematic review of lung function and COPD with peripheral blood DNA methylation in population based studies

Abstract

BackgroundEpigenetic variations in peripheral blood have potential as biomarkers for disease. This systematic review assesses the association of lung function and chronic obstructive pulmonary disease (COPD) with DNA methylation profiles in peripheral blood from population-based studies.MethodsOnline databases Medline, Embase, and Web of Science were searched. Google Scholar was searched to identify grey literature. After removing duplicate articles, 1155 articles were independently screened by two investigators. Peer reviewed reports on population-based studies that examined peripheral blood DNA methylation in participants with measured lung function (FEV1, FEV1/FVC ratio) or known COPD status were selected for full-text review. Six articles were suitable for inclusion. Information regarding study characteristics, designs, methodologies and conclusions was extracted. A narrative synthesis was performed based on published results.ResultsThree of the six articles assessed the association of COPD with DNA methylation, and two of these also included associations with lung function. Overall, five reports examined the association of lung function with DNA methylation profiles. Five of the six articles reported ‘significant’ results. However, no consistent CpG sites were identified across studies for COPD status or lung function values.ConclusionsDNA methylation patterns in peripheral blood from individuals with reduced lung function or COPD may be different to those in people with normal lung function. However, this systematic review did not find any consistent associations of lung function or COPD with differentially methylated CpG sites. Large studies with a longitudinal design to address reverse causality may prove a more fruitful area of research.Trial registrationPROSPERO 2016: CRD42016037352.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-017-0397-3) contains supplementary material, which is available to authorized users.

Tobacco-smoking induced GPR15-expressing T cells in blood do not indicate pulmonary damage

“…This partially agrees with epigenetic analysis of differentially methylated CpG sites in blood. A systematic review did not find any consistent association for lung function or COPD [ 39 ]. Furthermore, this site was not found to be smoking-specific in a Korean cohort of COPD patients [ 40 ].…”

Lung ageing and COPD: is there a role for ageing in abnormal tissue repair?

“…The majority of epigenome-wide methylation studies have been performed in whole blood, and few data are available on DNA methylation in whole lung tissue and lung tissue-specific cell types. Although it has been widely established that cigarette smoke affects DNA methylation [90] and that COPD is highly associated with cigarette smoke exposure, in a recent systematic review by MACHIN et al [91], no consistent differences were found in DNA methylation in peripheral blood in association with COPD or lung function. Therefore, the role of DNA methylation in COPD and hence the role of age-associated differences in DNA methylation in COPD remain unclear.…”

Identification of novel differentially methylated sites with potential as clinical predictors of impaired respiratory function and COPD

“…[7][8][9] Moreover, there has been little consistency between the positive findings reported. 9,10 Studies of lung tissue 5,8 have been constrained by sample availability, with the largest study to date comprising 160 subjects. 5 Inconsistency amongst the results of the peripheral bloodbased studies 3,6,7,9,11 is likely to be due to a number of factors, including small sample size (e.g., two studies had less than 200 samples) 6,11 and/or investigation of a relatively small number (~27,000) of CpG loci.…”

“…12 Differences in spirometric measures, definitions of COPD, study population characteristics and study design, in particular in the method used to adjust for smoking history, are also likely to be important sources of variation. 9,10 Here we sought to identify robust associations by assessing methylation in a large single cohort sample, applying a more rigorous correction for smoking history and by performing sensitivity analyses. In contrast to prior studies, we used the recently released Illumina EPIC array, which interrogates over 850,000 methylation sites.…”

“…The crosssectional design of prior studies has limited their capacity to distinguish cause and effect. 10 We mitigated this issue by testing our findings for their predictive power in an independent subpopulation of 150 participants with incident COPD who were free of disease at the time of blood sampling. Finally, where data were available, we attempted to replicate our EWAS and prediction findings in an independent cohort, LBC1936, drawn from the same population.…”