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Review: DNA methylation and alcohol use disorders: Progress and challenges.

ABSTRACT: Risk for alcohol use disorders (AUDs) is influenced by gene-environment interactions. Environmental factors can affect gene expression through epigenetic mechanisms such as DNA methylation. This review outlines the findings regarding the association of DNA methylation and AUDs.We searched PubMed (by April 2016) and identified 29 studies that examined the association of DNA methylation and AUDs. We also evaluated the methods used in these studies.Two studies demonstrated elevated global (repetitive element) DNA methylation levels in AUD subjects. Fifteen candidate gene studies showed hypermethylation of promoter regions of six genes (AVP, DNMT3B, HERP, HTR3A, OPRM1, and SNCA) or hypomethylation of the GDAP1 promoter region in AUD subjects. Five genome-wide DNA methylation studies demonstrated widespread DNA methylation changes across the genome in AUD subjects. Six studies showed significant correlations of DNA methylation with gene expression in AUD subjects. Three studies revealed interactive effects of genetic variation and DNA methylation on susceptibility to AUDs. Most studies analyzed AUD-associated DNA methylation changes in the peripheral blood; a few studies examined DNA methylation changes in postmortem brains of AUD subjects.Chronic alcohol consumption may result in DNA methylation changes, leading to neuroadaptations that may underlie some of the mechanisms of AUD risk and persistence. Future studies are needed to confirm the few existing results, and then to elucidate whether DNA methylation changes are the cause or consequence of AUDs.DNA methylation profiles may be used to assess AUD status or monitor AUD treatment response. (Am J Addict 2017;26:502-515).

SUBMITTER: Zhang H

PROVIDER: S-EPMC6003819 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Review: DNA methylation and alcohol use disorders: Progress and challenges.

Zhang Huiping H Gelernter Joel J

The American journal on addictions 20161019 5

<h4>Background and objectives</h4>Risk for alcohol use disorders (AUDs) is influenced by gene-environment interactions. Environmental factors can affect gene expression through epigenetic mechanisms such as DNA methylation. This review outlines the findings regarding the association of DNA methylation and AUDs.<h4>Methods</h4>We searched PubMed (by April 2016) and identified 29 studies that examined the association of DNA methylation and AUDs. We also evaluated the methods used in these studies. ...[more]

PMID: 27759945

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Project description:Recent studies in alcohol use disorders (AUDs) have demonstrated some connections between carnitine metabolism and the pathophysiology of the disease. In this scoping review, we aimed to collate and examine existing research available on carnitine metabolism and AUDs and develop hypotheses surrounding the role carnitine may play in AUD. A scoping review method was used to search electronic databases in September 2019. The database search terms used included "alcohol, alcoholism, alcohol abuse, alcohol consumption, alcohol drinking patterns, alcohol-induced disorders, alcoholic intoxication, alcohol-related disorders, binge drinking, Wernicke encephalopathy, acylcarnitine, acetyl-l-carnitine, acetylcarnitine, carnitine and palmitoylcarnitine." The inclusion criteria included English language, human-based, AUD diagnosis and measured blood or tissue carnitine or used carnitine as a treatment. Of 586 studies that were identified and screened, 65 underwent abstract review, and 41 were fully reviewed. Eighteen studies were ultimately included for analysis. Data were summarized in an electronic data extraction form. We found that there is limited literature available. Alcohol use appears to impact carnitine metabolism, most clearly in the setting of alcoholic cirrhosis. Six studies found carnitine to be increased in AUD, of which 5 were conducted in patients with alcoholic cirrhosis. Only 3 placebo-controlled trials were identified and provide some support for the use of carnitine in AUD to decrease cravings, anhedonia, and withdrawal and improve cognition. The increase in plasma carnitine in alcoholic cirrhosis may be related to disordered fatty acid metabolism and oxidative stress that occurs in AUD. The multiple possible therapeutic effects carnitine could have on ethanol metabolism and the early evidence available for carnitine supplementation as a treatment for AUD provide a foundation for future randomized control trials of carnitine for treating AUD.

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Review: DNA methylation and alcohol use disorders: Progress and challenges.

Publications

Review: DNA methylation and alcohol use disorders: Progress and challenges.

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