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酒精戒断期间全球甲基化和羟甲基化的短期变化。

Short-term changes in global methylation and hydroxymethylation during alcohol detoxification.

机构信息

Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Nussbaumstraße 7, D - 80336 Munich, Germany.

Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Nussbaumstraße 7, D - 80336 Munich, Germany.

出版信息

Eur Neuropsychopharmacol. 2019 Jul;29(7):897-903. doi: 10.1016/j.euroneuro.2019.05.001. Epub 2019 May 25.

Abstract

Alcohol dependence is a common public health problem and epigenetics may offer new aspects in understanding the biological and genetic underpinnings and improve treatment of this complex disease. Supposedly, methylation and hydroxymethylation are altered in brain tissues and in synapse-related genes due to chronic alcohol intake and during withdrawal. To assess potential epigenetic changes after cessation of chronic alcohol intake, we compared 23 alcohol-dependent individuals during inpatient alcohol detoxification with 13 carefully matched controls. Blood samples were taken on the day of admission, after one and after two weeks at the end of inpatient treatment. Genome-wide global methylation and global DNA hydroxymethylation were compared across groups. There were significant differences in global methylation across time from admission to one and two weeks of inpatient withdrawal (p < 0.001). These findings were paralleled to changes in global DNA hydroxymethylation across time when age was employed as a cofactor (p < 0.001). Several potentially influencing variables like severity of withdrawal, dose of withdrawal medication and alcohol intake before admission did not yield significant influence on epigenetic changes. The results confirm previous findings of significant alterations of epigenetic patterns during alcohol intoxication and present for the first time hydroxymethylation changes in these individuals.

摘要

酒精依赖是一个常见的公共健康问题,表观遗传学可能为理解这种复杂疾病的生物学和遗传学基础提供新的视角,并改善其治疗方法。据推测,由于长期饮酒和戒断期间,脑组织和突触相关基因中的甲基化和羟甲基化发生改变。为了评估慢性酒精摄入停止后的潜在表观遗传变化,我们比较了 23 名住院酒精戒断的酒精依赖者与 13 名精心匹配的对照者。在住院治疗结束时,分别在入院当天、第 1 天和第 2 天采集血样。对各组进行全基因组整体甲基化和整体 DNA 羟甲基化比较。从入院到住院戒断 1 周和 2 周的时间,整体甲基化存在显著差异(p<0.001)。当年龄作为协变量时,整体 DNA 羟甲基化在时间上的变化也呈现出相似的趋势(p<0.001)。一些潜在的影响变量,如戒断严重程度、戒断药物剂量和入院前饮酒量,对表观遗传变化没有显著影响。这些结果证实了之前在酒精中毒期间表观遗传模式发生显著改变的发现,并首次提出了这些个体中羟甲基化改变的情况。

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