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Cigarette Smoking Reduces DNA Methylation Levels at Multiple Genomic Loci but the Effect is Partially Reversible upon Cessation

ABSTRACT: DNA methylation is an epigenetic event whose pattern is altered frequently in a wide variety of human diseases. Smoking affects DNA methylation possibly leading to abnormal expression of a broad spectrum of genes which in turn may result to the various side effects and diseases associated with smoking. The long term effects of smoking have been widely studied but the mechanism(s) by which those effects may be reversible by smoking cessation are not clearly understood. Here, we conducted an epigenome-wide association study in peripheral-blood DNA in 464 individuals who were current, former and never-smokers. We identified 15 distinct loci (10 of which were novel) where DNA methylation was reduced in smokers and was reversed (but did not reach non-smoking levels) upon smoking cessation within 12 weeks. Although the functional impact of this reversal of DNA methylation is still not understood, this study illustrates the potential of epigenomics to provide insights into mechanisms of environmental and lifestyle exposures, and to suggest new avenues for clinical intervention

ORGANISM(S): Homo sapiens

PROVIDER: GSE50660 | GEO | 2014/11/25

SECONDARY ACCESSION(S): PRJNA218212

REPOSITORIES: GEO

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Project description:Background: Epigenetics is involved in various human diseases. Smoking is one of the most common environmental factors causing epigenetic changes. The DNA methylation changes and mechanisms after quitting smoking have not yet been defined. The present study examined the changes in DNA methylation level before and after short-term smoking cessation and explored the potential mechanism. Methods: Whole blood and clinical data were collected in 8 patients before and after short-term smoking cessation, DNA methylation was assessed, and differentially methylated sites were analyzed, followed by a comprehensive analysis of the differentially methylated sites with clinical data. GO/KEGG enrichment and protein-protein interaction (PPI) network identified the hub genes. The differentially methylated sites were detected by GEO2R between former smoking and current smoking in GSE50660 from the GEO database. Then, a Venn analysis was carried out using the differentially methylated sites. GO/KEGG enrichment analysis was performed on the genes corresponding to the common DNA methylation sites, the PPI network was constructed, and hub genes were predicted. The enriched genes associated with the cell cycle were selected, and the gene expression was analyzed in pan-cancer based on the TCGA database. Results: Most of the DNA methylation levels were decreased after short-term smoking cessation; a total of 694 hypermethylated CPG sites and 3184 hypomethylated CPG sites were identified. The DNA methylation levels altered according to the clinical data (body weight, expiratory, and tobacco dependence score). Enrichment analysis, construction of PPI network, and pan-cancer analysis suggested that smoking cessation may be involved in various biological processes. Conclusions: Smoking cessation leads to epigenetic changes, mainly observed in the decline of most DNA methylation levels. Bioinformatics further identified the biologically relevant changes after short-term smoking cessation.

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Cigarette Smoking Reduces DNA Methylation Levels at Multiple Genomic Loci but the Effect is Partially Reversible upon Cessation

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