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The Effect of Citalopram on Genome-Wide DNA Methylation of Human Cells

机译：西酞普兰对人细胞全基因组DNA甲基化的影响

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Commonly used pharmaceutical drugs might alter the epigenetic state of cells, leading to varying degrees of long-term repercussions to human health. To test this hypothesis, we cultured HEK-293 cells in the presence of 50a????M citalopram, a common antidepressant, for 30 days and performed whole-genome DNA methylation analysis using the NimbleGen Human DNA Methylation 3x720K Promoter Plus CpG Island Array. A total of 626 gene promoters, out of a total of 25,437 queried genes on the array (2.46%), showed significant differential methylation (); among these, 272 were hypomethylated and 354 were hypermethylated in treated versus control. Using Ingenuity Pathway Analysis, we found that the chief gene networks and signaling pathways that are differentially regulated include those involved in nervous system development and function and cellular growth and proliferation. Genes implicated in depression, as well as genetic networks involving nucleic acid metabolism, small molecule biochemistry, and cell cycle regulation were significantly modified. Involvement of upstream regulators such as BDNF, FSH, and NF?oB was predicted based on differential methylation of their downstream targets. The study validates our hypothesis that pharmaceutical drugs can have off-target epigenetic effects and reveals affected networks and pathways. We view this study as a first step towards understanding the long-term epigenetic consequences of prescription drugs on human health.
机译：常用的药物可能会改变细胞的表观遗传状态，从而对人体健康造成不同程度的长期影响。为了检验这一假设，我们在常见抗抑郁药50a？西酞普兰存在下培养HEK-293细胞30天，并使用NimbleGen人类DNA甲基化3x720K Promoter Plus CpG Island Array进行全基因组DNA甲基化分析。 。阵列中总共25,437个被查询的基因中，共有626个基因启动子（2.46％）显示出显着的甲基化差异（）。其中，与对照相比，其中272个被低甲基化，而354个被高甲基化。使用“机能途径分析”，我们发现受到差异调节的主要基因网络和信号传导途径包括涉及神经系统发育和功能以及细胞生长和增殖的那些。涉及抑郁症的基因，以及涉及核酸代谢，小分子生物化学和细胞周期调控的遗传网络都得到了显着修饰。基于下游调节剂的下游甲基化差异，可以预测上游调节剂（如BDNF，FSH和NF？oB）的参与。这项研究证实了我们的假设，即药物可能具有脱靶表观遗传效应，并揭示了受影响的网络和途径。我们认为这项研究是了解处方药对人类健康的长期表观遗传学后果的第一步。

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