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.
Highlights
Epigenetic variations in peripheral blood have potential as biomarkers for disease
Epigenetics is the regulation of gene expression which is independent of the underlying Deoxyribonucleic acid (DNA) sequence, and is instead brought about by modifications to histones, changes in chromatin structure, microRNAs, noncoding RNAs, and DNA methylation
Variation in methylation in response to smoking has been reported in several 5’-cytosine-phosphate-guanine-3’ sequence (CpG) island (CGI) [16], which may reverse with smoking cessation [17], but methylation markers for chronic obstructive pulmonary disease (COPD) and lung function have only been explored in a few studies
Summary
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. The use of DNA methylation profiles in peripheral blood as a biomarker for risk of disease, risk of disease progression, response to therapy and as a biomarker of exposure to environmental insults that may influence disease is an attractive concept as it could be translated into clinical practice with relative ease. Chronic obstructive pulmonary disease (COPD) is estimated to affect 334 million people worldwide [7, 8] with a global prevalence of 11.7%. It ranks 9th in the all-cause global disability-adjusted life-years lost. Variation in methylation in response to smoking has been reported in several CGIs [16], which may reverse with smoking cessation [17], but methylation markers for COPD and lung function have only been explored in a few studies
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