Dataset Information

Global DNA methylation levels in white blood cells of patients with chronic heroin use disorder. A prospective study.

ABSTRACT:

Background

Increasing scientific evidence shows the significant role of epigenetic mechanisms in drug use disorder, abstinence and relapse. Studies on human subjects are limited compared to those on animals, for various reasons such as poly-substance abuse, high drop-out rate and technical difficulties.

Objectives

Our goal was to evaluate whether a monitored abstinence period of 21 days could induce changes in global DNA methylation in chronic heroin users.

Method

In the current study, we present data on global DNA methylation on a set of 18 male patients with chronic heroin use disorder, carefully selected based on inclusion and exclusion criteria, who were hospitalized and closely monitored during a 21-day detoxification program, one of the few where no opioid agonist is administered. The participants were sampled twice, once upon enrolment to the program and once upon completion.

Results

According to our results, no difference in global DNA methylation was detected between samples collected upon enrolment and samples collected upon completion of the program.

Conclusion

The findings of this study do not rule out the possibility that the 21-day abstinence period was not long enough to observe changes in global DNA methylation, or that abstinence induced site-specific methylation changes (but not global changes), that certainly merit further evaluation.

SUBMITTER: Fragou D

PROVIDER: S-EPMC7892979 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Global DNA methylation levels in white blood cells of patients with chronic heroin use disorder. A prospective study.

Fragou Domniki D Chao Mu-Rong MR Hu Chiung-Wen CW Nikolaou Kakia K Kovatsi Leda L

Toxicology reports 20210206

<h4>Background</h4>Increasing scientific evidence shows the significant role of epigenetic mechanisms in drug use disorder, abstinence and relapse. Studies on human subjects are limited compared to those on animals, for various reasons such as poly-substance abuse, high drop-out rate and technical difficulties.<h4>Objectives</h4>Our goal was to evaluate whether a monitored abstinence period of 21 days could induce changes in global DNA methylation in chronic heroin users.<h4>Method</h4>In the cu ...[more]

PMID: 33643851

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Project description:BackgroundEpigenetics, particularly DNA methylation, has recently been elucidated as important in gastric cancer (GC) initiation and progression. We investigated the clinical and prognostic importance of whole blood global and site-specific DNA methylation in GC.MethodsGenomic DNA was extracted from the peripheral blood of 105 Omani GC patients at diagnosis. DNA methylation was quantified by pyrosequencing of global DNA and specific gene promoter regions at 5 CpG sites for CDH1, 7 CpG sites for p16, 4 CpG sites for p53, and 3 CpG sites for RUNX3. DNA methylation levels in patients were categorized into low, medium, and high tertiles. Associations between methylation level category and clinicopathological features were evaluated using ?(2) tests. Survival analyses were carried out using the Kaplan-Meier method and log rank test. A backward conditional Cox proportional hazards regression model was used to identify independent predictors of survival.ResultsOlder GC patients had increased methylation levels at specific CpG sites within the CDH1, p53, and RUNX-3 promoters. Male gender was significantly associated with reduced global and increased site-specific DNA methylation levels in CDH1, p16, and p53 promoters. Global DNA low methylation level was associated with better survival on univariate analysis. Patients with high and medium methylation vs. low methylation levels across p16 promoter CpG sites, site 2 in particular, had better survival. Multivariate analysis showed that global DNA hypermethylation was a significant independent predictor of worse survival (hazard ratio (HR)?= 2.0, 95% CI: 1.1-3.8; p = 0.02) and high methylation mean values across p16 promoter sites 1-7 were associated with better survival with HR of 0.3 (95% CI, 0.1-0.8; p = 0.02) respectively.ConclusionsAnalysis of global and site-specific DNA methylation in peripheral blood by pyrosequencing provides quantitative DNA methylation values that may serve as important prognostic indicators.

Project description:ImportanceHeroin use is an urgent concern in the United States. Little is know about the course of heroin use, heroin use disorder, and associated factors.ObjectiveTo examine changes in the lifetime prevalence, patterns, and associated demographics of heroin use and use disorder from 2001-2002 to 2012-2013 in 2 nationally representative samples of the US adult general population.Design, setting, and participantsThis survey study included data from 43 093 respondents of the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) and 36 309 respondents of the 2012-2013 NESARC-III. Data were analyzed from February 2 to September 15, 2016.Main outcomes and measuresLifetime heroin use and DSM-IV heroin use disorder.ResultsAmong the 79 402 respondents (43.3% men; 56.7% women; mean [SD] age, 46.1 [17.9] years), prevalence of heroin use and heroin use disorder significantly increased from 2001-2002 to 2012-2013 (use: 0.33% [SE, 0.03%] vs 1.6% [SE, 0.08%]; disorder: 0.21% [SE, 0.03%] vs 0.69% [SE, 0.06%]; P < .001). The increase in the prevalence of heroin use was significantly pronounced among white (0.34% [SE, 0.04%] in 2001-2002 vs 1.90% [SE, 0.12%] in 2012-2013) compared with nonwhite (0.32% [SE, 0.05%] in 2001-2002 vs 1.05% [SE, 0.10%] in 2012-2013; P < .001) individuals. The increase in the prevalence of heroin use disorder was more pronounced among white individuals (0.19% [SE, 0.03%] in 2001-2002 vs 0.82% [SE, 0.08%] in 2012-2013; P < .001) and those aged 18 to 29 (0.21% [SE, 0.06%] in 2001-2002 vs 1.0% [0.17%] in 2012-2013; P = .01) and 30 to 44 (0.20% [SE, 0.04%] in 2001-2002 vs 0.77% [0.10%] in 2012-2013; P = .03) years than among nonwhite individuals (0.25% [SE, 0.04%] in 2001-2002 vs 0.43% [0.07%] in 2012-2013) and older adults (0.22% [SE, 0.04%] in 2001-2002 vs 0.51% [SE, 0.07%] in 2012-2013). Among users, significant differences were found across time in the proportion of respondents meeting DSM-IV heroin use disorder criteria (63.35% [SE, 4.79%] in 2001-2001 vs 42.69% [SE, 2.87%] in 2012-2013; P < .001). DSM-IV heroin abuse was significantly more prevalent among users in 2001-2002 (37.02% [SE, 4.67%]) than in 2012-2013 (19.19% [SE, 2.34%]; P = .001). DSM-IV heroin dependence among users was similar in 2001-2002 (28.22% [SE, 3.95%]) and in 2012-2013 (25.02% [SE, 2.20%]; P = .48). The proportion of those reporting initiation of nonmedical use of prescription opioids before initiating heroin use increased across time among white individuals (35.83% [SE, 6.03%] in 2001-2002 to 52.83% [SE, 2.88%] in 2012-2013; P = .01).Conclusions and relevanceThe prevalence of heroin use and heroin use disorder increased significantly, with greater increases among white individuals. The nonmedical use of prescription opioids preceding heroin use increased among white individuals, supporting a link between the prescription opioid epidemic and heroin use in this population. Findings highlight the need for educational campaigns regarding harms related to heroin use and the need to expand access to treatment in populations at increased risk for heroin use and heroin use disorder.

Dataset Information

Global DNA methylation levels in white blood cells of patients with chronic heroin use disorder. A prospective study.

Background

Objectives

Method

Results

Conclusion

Publications

Global DNA methylation levels in white blood cells of patients with chronic heroin use disorder. A prospective study.

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