Dataset Information

Opposite Epigenetic Associations With Alcohol Use and Exercise Intervention.

ABSTRACT: Alcohol use disorder (AUD) is a devastating public health problem in which both genetic and environmental factors play a role. Growing evidence supports that epigenetic regulation is one major mechanism in neuroadaptation that contributes to development of AUD. Meanwhile, epigenetic patterns can be modified by various stimuli including exercise. Thus, it is an intriguing question whether exercise can lead to methylation changes that are opposite to those related to drinking. We herein conducted a comparative study to explore this issue. Three cohorts were profiled for DNA methylation (DNAm), including a longitudinal exercise intervention cohort (53 healthy participants profiled at baseline and after a 12-months exercise intervention), a cross-sectional case-control cohort (81 hazardous drinkers and 81 healthy controls matched in age and sex), and a cross-sectional binge drinking cohort (281 drinkers). We identified 906 methylation sites showing significant DNAm differences between drinkers and controls in the case-control cohort, as well as, associations with drinking behavior in the drinking cohort. In parallel, 341 sites were identified for significant DNAm alterations between baseline and follow-up in the exercise cohort. Thirty-two sites overlapped between these two set of findings, of which 15 sites showed opposite directions of DNAm associations between exercise and drinking. Annotated genes of these 15 sites were enriched in signaling pathways related to synaptic plasticity. In addition, the identified methylation sites significantly associated with impaired control over drinking, suggesting relevance to neural function. Collectively, the current findings provide preliminary evidence that exercise has the potential to partially reverse DNAm differences associated with drinking at some CpG sites, motivating rigorously designed longitudinal studies to better characterize epigenetic effects with respect to prevention and intervention of AUD.

SUBMITTER: Chen J

PROVIDER: S-EPMC6249510 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Opposite Epigenetic Associations With Alcohol Use and Exercise Intervention.

Chen Jiayu J Hutchison Kent E KE Bryan Angela D AD Filbey Francesca M FM Calhoun Vince D VD Claus Eric D ED Lin Dongdong D Sui Jing J Du Yuhui Y Liu Jingyu J

Frontiers in psychiatry 20181115

Alcohol use disorder (AUD) is a devastating public health problem in which both genetic and environmental factors play a role. Growing evidence supports that epigenetic regulation is one major mechanism in neuroadaptation that contributes to development of AUD. Meanwhile, epigenetic patterns can be modified by various stimuli including exercise. Thus, it is an intriguing question whether exercise can lead to methylation changes that are opposite to those related to drinking. We herein conducted ...[more]

PMID: 30498460

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Project description:IntroductionHuman and nonhuman animal research suggests that greater oxytocin (OT) activity is protective against harmful substance use. Most research on this topic is preclinical, with few studies evaluating the association between substance use and individual differences in the human OT system. The present study sought to fill this gap by evaluating the relationship between alcohol use and multiple biological measures of OT activity in an overall low to moderate-drinking sample.MethodAs part of a larger study, generally healthy young (n = 51) and older (n = 53) adults self-reported whether they regularly used alcohol and how much alcohol they consumed per week. Participants also provided blood samples from which peripheral OT, and in an age-heterogeneous subset of participants (n = 56) variation in the oxytocin receptor gene (the OXTR rs53576 polymorphism) and OXTR DNA methylation levels (at cytosine-guanine dinucleotide sites -860, -924, -934), were obtained.ResultsA-allele carriers of the OXTR rs53579 polymorphism were less likely to regularly consume alcohol. Among regular alcohol consumers, number of alcoholic drinks per week was positively associated with peripheral OT in regression models excluding observations of high influence (postdiagnostic models). Number of alcoholic drinks per week was consistently negatively associated with OXTR DNA methylation at site -860; and with OXTR DNA methylation at site -924 in postdiagnostic models.ConclusionsThe significant associations between alcohol use and individual differences in OT activity support the involvement of the OT system in alcohol use, which most likely reflect the role of OT when alcohol use is under control of its rewarding properties and/or the acute impacts of alcohol on the OT system. Additional research with markers of OT activity and alcohol use, particularly longitudinal, is needed to clarify the bidirectional effects of OT and alcohol use in moderate to harmful drinking and dependence.

Dataset Information

Opposite Epigenetic Associations With Alcohol Use and Exercise Intervention.

Publications

Opposite Epigenetic Associations With Alcohol Use and Exercise Intervention.

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