DNA methylation signatures of chronic alcohol dependence in purified CD3+ T-cells of patients undergoing alcohol treatment

Abstract

Several studies have shown an association of alcohol dependence with DNA methylation (DNAm), suggesting that environmentally-induced changes on epigenomic variation may play an important role in alcohol dependence. In the present study, we analysed genome-wide DNAm profiles of purified CD3+ T-cells from pre- and post-treatment alcohol dependent patients, as well as closely matched healthy controls. We identified 59 differentially methylated CpG sites comparing patients prior to treatment with healthy controls and were able to confirm 8 of those sites in additional analyses for differentially methylated regions. Comparing patients before and after a 3-week alcohol treatment program we revealed another unique set of 48 differentially methylated CpG sites. Additionally, we found that the mean global DNAm was significantly lower in patients prior to treatment compared to controls, but reverted back to levels similar to controls after treatment. We validated top-ranked hits derived from the epigenome-wide analysis by pyrosequencing and further replicated two of them in an independent cohort and confirmed differential DNAm of HECW2 and SRPK3 in whole blood. This study is the first to show widespread DNAm variation in a disease-relevant blood cell type and implicates HECW2 and SRPK3 DNAm as promising blood-based candidates to follow up in future studies.

Acute alcohol withdrawal and recovery in men lead to profound changes in DNA methylation profiles: a longitudinal clinical study

“…Additionally, alcohol is a potent agent, and the observed differences between patients and controls may demonstrate the strong effect of alcohol consumption, an effect which is reduced after cessation of drinking but continues to be observable long afterwards . In particular, our results are in line with studies showing pronounced differences between patients in acute withdrawal and after 2 weeks of recovery .…”

“…They show that the degree of DNAm diminishes after a 30‐day in‐patient treatment program. Another EWAS further included a comparison of DNAm changes in 24 patients prior to and after a 3‐week detoxification program and 23 controls . At a DNAm difference of > 5%, 59 CpG sites were differentially methylated between patients and controls before entering the treatment program and 48 CpG sites were differentially methylated comparing patients before and after treatment.…”

Transcriptional Regulators as Targets for Alcohol Pharmacotherapies

“…Many of the differentially methylated cytosines identified between controls and alcohol-dependent subjects were reversed during abstinence to levels similar to controls. Similarly, Bruckmann et al (Bruckmann et al 2017) found that some of the differentially methylated cytosines identified in CD3+ T cells between healthy controls and alcohol-dependent patients reverted back to control levels after abstinence, demonstrating a potential causal role for alcohol in changing DNAm in blood cells.…”

Prospects of Genetics and Epigenetics of Alcohol Use Disorder

“…In a longitudinal study of 165 female participants, different degrees of alcohol consumption over the past 6 months were found to be associated with two loci reaching epigenome-wide significance [37]. Another EWAS compared methylation patterns in 24 patients before and after a 3-week detoxification program and 23 controls [38]. Here, 59 CpG sites were differentially methylated between patients and controls before entering the treatment program and 48 CpG sites were differentially methylated comparing patients before and after treatment [38].…”

“…Another EWAS compared methylation patterns in 24 patients before and after a 3-week detoxification program and 23 controls [38]. Here, 59 CpG sites were differentially methylated between patients and controls before entering the treatment program and 48 CpG sites were differentially methylated comparing patients before and after treatment [38].…”