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Review
. 2015 Oct 16:7:113.
doi: 10.1186/s13148-015-0148-3. eCollection 2015.

DNA methylation changes of whole blood cells in response to active smoking exposure in adults: a systematic review of DNA methylation studies

Xu Gao  1 , Min Jia  1 , Yan Zhang  1 , Lutz Philipp Breitling  1 , Hermann Brenner  2
Affiliations
Review

DNA methylation changes of whole blood cells in response to active smoking exposure in adults: a systematic review of DNA methylation studies

Xu Gao et al. Clin Epigenetics. .

Abstract

Active smoking is a major preventable public health problem and an established critical factor for epigenetic modification. In this systematic review, we identified 17 studies addressing the association of active smoking exposure with methylation modifications in blood DNA, including 14 recent epigenome-wide association studies (EWASs) and 3 gene-specific methylation studies (GSMSs) on the gene regions identified by EWASs. Overall, 1460 smoking-associated CpG sites were identified in the EWASs, of which 62 sites were detected in multiple (≥3) studies. The three most frequently reported CpG sites (genes) in whole blood samples were cg05575921 (AHRR), cg03636183 (F2RL3), and cg19859270 (GPR15), followed by other loci within intergenic regions 2q37.1 and 6p21.33. These significant smoking-related genes were further assessed by specific methylation assays in three GSMSs and reflected not only current but also lifetime or long-term exposure to active smoking. In conclusion, this review summarizes the evidences for the use of blood DNA methylation patterns as biomarkers of smoking exposure for research and clinical practice. In particular, it provides a reservoir for constructing a smoking exposure index score which could be used to more precisely quantify long-term smoking exposure and evaluate the risks of smoking-induced diseases.

Keywords: Active smoking; DNA methylation; Systematic review; Whole blood cells.

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Figures

Fig. 1
Fig. 1
Flow diagram of systematic literature search in PubMed and Web of Science
Fig. 2
Fig. 2
Effect sizes of smoking-related CpG sites reported ≥3 times (beta values of independent validation samples are shown where available). Chr chromosome position, triangles and dots represent the mean and median of beta values, respectively
Fig. 3
Fig. 3
Effect sizes of smoking-induced methylation for current smokers and former smokers compared with non-smokers. Chr chromosome position, used the publically available data of Zeilinger et al. (median beta values) [6]
See this image and copyright information in PMC

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