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BMC Genomics. 2017 Oct 18;18(1):805. doi: 10.1186/s12864-017-4198-0.

The dynamics of smoking-related disturbed methylation: a two time-point study of methylation change in smokers, non-smokers and former smokers.

Author information

1
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764, Neuherberg, Bavaria, Germany. rory.wilson@helmholtz-muenchen.de.
2
Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764, Neuherberg, Bavaria, Germany. rory.wilson@helmholtz-muenchen.de.
3
Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Research Unit Molecular Epidemiology (AME), Ingolstädter Landstr. 1, D-85764, Neuherberg, Germany. rory.wilson@helmholtz-muenchen.de.
4
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764, Neuherberg, Bavaria, Germany.
5
Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764, Neuherberg, Bavaria, Germany.
6
German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Bavaria, Germany.
7
Environmental Public Health Division, US Environmental Protection Agency, Chapel Hill, NC, 27514, USA.
8
DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Bavaria, Germany.

Abstract

BACKGROUND:

The evidence for epigenome-wide associations between smoking and DNA methylation continues to grow through cross-sectional studies. However, few large-scale investigations have explored the associations using observations for individuals at multiple time-points. Here, through the use of the Illumina 450K BeadChip and data collected at two time-points separated by approximately 7 years, we investigate changes in methylation over time associated with quitting smoking or remaining a former smoker, and those associated with continued smoking.

RESULTS:

Our results indicate that after quitting smoking the most rapid reversion of altered methylation occurs within the first two decades, with reversion rates related to the initial differences in methylation. For 52 CpG sites, the change in methylation from baseline to follow-up is significantly different for former smokers relative to the change for never smokers (lowest p-value 3.61 x 10-39 for cg26703534, gene AHRR). Most of these sites' respective regions have been previously implicated in smoking-associated diseases. Despite the early rapid change, dynamism of methylation appears greater in former smokers vs never smokers even four decades after cessation. Furthermore, our study reveals the heterogeneous effect of continued smoking: the methylation levels of some loci further diverge between smokers and non-smokers, while others re-approach. Though intensity of smoking habit appears more significant than duration, results remain inconclusive.

CONCLUSIONS:

This study improves the understanding of the dynamic link between cigarette smoking and methylation, revealing the continued fluctuation of methylation levels decades after smoking cessation and demonstrating that continuing smoking can have an array of effects. The results can facilitate insights into the molecular mechanisms behind smoking-induced disturbed methylation, improving the possibility for development of biomarkers of past smoking behavior and increasing the understanding of the molecular path from exposure to disease.

KEYWORDS:

Cigarettes; DNA methylation; Epigenetics; Longitudinal study; Smoking; Tobacco

PMID:
29047347
DOI:
10.1186/s12864-017-4198-0
[Indexed for MEDLINE]
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