Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health

Abstract

BackgroundTobacco 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.MethodsWe 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.ResultsWe 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (10.1186/s13148-018-0558-0) contains supplementary material, which is available to authorized users.

MiR-30a and miR-379 modulate retinoic acid pathway by targeting DNA methyltransferase 3B in oral cancer

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Heritability of skewed X-inactivation in female twins is tissue-specific and dependent on age

“…We reasoned that changes of XCI patterns may result from smoking, and affect in turn short-term and long-term health. In order to test our hypothesis, we used the 270 individuals in our dataset for which we had smoking status at the time of sample collection, including 233 never smokers and 37 current smokers 45 . We found no difference in the frequency of skewed XCI patterns between never and current smokers (36% and 35% respectively) in LCLs.…”

“…Association between the degree of skewing in LCLs and self-reported smoking status was tested in the 270 individuals with reliable smoking status recorded 45 . Dataset included 270 females classified either as current smokers (N = 37) or never smokers (N = 233; Table S2).…”

Sensitive to the effects of environmental factors miR-638 and common diseases

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