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Smoking-associated DNA methylation features link to HIV outcomes [HumanMethylation450 BeadChip]

ABSTRACT: Smoking is common in people who live with HIV infection and has significant adverse effects on HIV outcomes. The impacts of smoking on methylome has been well established in non-HIV populations. However, the smoking’s effects on host methylome in HIV-positive population has not been investigated and it is unknown if smoking-associated DNA methylation link to HIV outcomes. In this study, we applied machine learning methods selected smoking-associated DNA methylation features to predict HIV related frailty and mortality.

ORGANISM(S): Homo sapiens

PROVIDER: GSE117859 | GEO | 2019/07/23

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.

Project description:Waterpipe (also called hookah, shisha, or narghile) smoking is a common form of tobacco use in the Middle East. Its use is becoming more prevalent in Western societies, especially among young adults as an alternative form of tobacco use to traditional cigarettes. While the risk to cigarette smoking is well documented, the risk to waterpipe smoking is not well defined with limited information on its health impact at the epidemiologic, clinical and biologic levels with respect to lung disease. Based on the knowledge that airway epithelial cell DNA methylation is modified in response to cigarette smoke and in cigarette smoking-related lung diseases, we assessed the impact of light-use water-pipe smoking on DNA methylation of the small airway epithelium (SAE) and whether changes in methylation were linked to the transcriptional output of the cells. Small airway epithelium was obtained from 7 nonsmokers and 7 light-use (2.6 ± 1.7 sessions/wk) waterpipe-only smokers. Genome-wide comparison of SAE DNA methylation of waterpipe smokers to nonsmokers identified 727 probesets differentially methylated (fold-change >1.5, p<0.05) representing 673 unique genes. Dominant pathways associated with these epigenetic changes include those linked to G-protein coupled receptor signaling, aryl hydrocarbon receptor signaling and xenobiotic metabolism signaling, all of which have been associated with cigarette smoking and lung disease. Of the genes differentially methylated, 11.3% exhibited a corresponding significant (p<0.05) change in gene expression with enrichment in pathways related to regulation of mRNA translation and protein synthesis (eIF2 signaling and regulation of eIF4 and p70S6K signaling). Overall, these data demonstrate that light-use waterpipe smoking is associated with epigenetic changes and related transcriptional modifications in the SAE, the cell population demonstrating the earliest pathologic abnormalities associated with chronic cigarette smoking. This study demonstrates that light-use waterpipe smoking in young adults is associated with a broad range of genome-wide DNA methylation-related changes of the SAE impacting a number of genes linked to pathways previously associated with cigarette smoking. Further, many of these methylation-related changes correlate with waterpipe smoking-associated changes in the SAE transcriptome. Together, these data add to the accumulating evidence that waterpipe smoking is harmful, and may lead to lung disease.

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Smoking-associated DNA methylation features link to HIV outcomes [HumanMethylation450 BeadChip]

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