DNA methylation signatures of chronic alcohol dependence in purified CD3+ T-cells of patients undergoing alcohol treatment
DNA methylation signatures of chronic alcohol dependence in purified CD3+ T-cells of patients undergoing alcohol treatment
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DOI：
10.1038/s41598-017-06847-z
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发表时间：
2017-07-26
影响因子：
4.6
通讯作者：
Nieratschker, Vanessa
中科院分区：
文献类型：
--
作者：
Brueckmann, Christof;Islam, Sumaiya A.;Nieratschker, Vanessa
一些研究表明酒精依赖与DNA甲基化（DNAm）相关，表明环境诱导的表观基因组变异变化可能在酒精依赖中起重要作用。在本研究中，我们分析了酒精依赖患者治疗前后纯化的CD3（+）T细胞的全基因组DNA图谱，以及密切匹配的健康对照。我们确定了59个差异甲基化的CpG位点，将治疗前的患者与健康对照进行比较，并能够在对差异甲基化区域的额外分析中确认其中8个位点。通过比较3周酒精治疗前后的患者，我们发现了另一组独特的48个差异甲基化CpG位点。此外，我们发现，与对照组相比，治疗前患者的平均总体DNAm显著降低，但治疗后恢复到与对照组相似的水平。我们通过焦磷酸测序验证了来自表观基因组全分析的排名靠前的命中，并在独立队列中进一步复制了其中两个命中，并确认了全血中HECW2和SRPK3的差异DNA m。这项研究是第一个显示疾病相关血细胞类型中广泛的DNAm变异，并暗示HECW2和SRPK3 DNAm是未来研究中有希望的血液候选者。
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.