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Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health.
- Source :
-
Clinical epigenetics [Clin Epigenetics] 2018 Oct 20; Vol. 10 (1), pp. 126. Date of Electronic Publication: 2018 Oct 20. - Publication Year :
- 2018
-
Abstract
- Background: Tobacco smoking is a risk factor for multiple diseases, including cardiovascular disease and diabetes. Many smoking-associated signals have been detected in the blood methylome, but the extent to which these changes are widespread to metabolically relevant tissues, and impact gene expression or metabolic health, remains unclear.<br />Methods: We investigated smoking-associated DNA methylation and gene expression variation in adipose tissue biopsies from 542 healthy female twins. Replication, tissue specificity, and longitudinal stability of the smoking-associated effects were explored in additional adipose, blood, skin, and lung samples. We characterized the impact of adipose tissue smoking methylation and expression signals on metabolic disease risk phenotypes, including visceral fat.<br />Results: We identified 42 smoking-methylation and 42 smoking-expression signals, where five genes (AHRR, CYP1A1, CYP1B1, CYTL1, F2RL3) were both hypo-methylated and upregulated in current smokers. CYP1A1 gene expression achieved 95% prediction performance of current smoking status. We validated and replicated a proportion of the signals in additional primary tissue samples, identifying tissue-shared effects. Smoking leaves systemic imprints on DNA methylation after smoking cessation, with stronger but shorter-lived effects on gene expression. Metabolic disease risk traits such as visceral fat and android-to-gynoid ratio showed association with methylation at smoking markers with functional impacts on expression, such as CYP1A1, and at tissue-shared smoking signals, such as NOTCH1. At smoking-signals, BHLHE40 and AHRR DNA methylation and gene expression levels in current smokers were predictive of future gain in visceral fat upon smoking cessation.<br />Conclusions: Our results provide the first comprehensive characterization of coordinated DNA methylation and gene expression markers of smoking in adipose tissue. The findings relate to human metabolic health and give insights into understanding the widespread health consequence of smoking outside of the lung.
- Subjects :
- Adult
Aged
Blood Proteins genetics
Cytochrome P-450 CYP1A1 genetics
Cytochrome P-450 CYP1B1 genetics
Cytokines genetics
Epigenesis, Genetic
Female
Gene Expression Regulation
Healthy Volunteers
Humans
Male
Middle Aged
Receptor, Notch1 genetics
Receptors, Thrombin
Adipose Tissue chemistry
DNA Methylation
Gene Expression Profiling methods
Smoking genetics
Twins genetics
Up-Regulation
Subjects
Details
- Language :
- English
- ISSN :
- 1868-7083
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Clinical epigenetics
- Publication Type :
- Academic Journal
- Accession number :
- 30342560
- Full Text :
- https://doi.org/10.1186/s13148-018-0558-0