Human Molecular Genetics Laboratory, Rajiv Gandhi Centre for Biotechnology, Trivandrum, Kerala, India.
Mental Health Centre, Trivandrum, Kerala, India.
Epigenomics. 2018 Mar;10(3):233-247. doi: 10.2217/epi-2017-0086. Epub 2018 Jan 18.
The present study intends to evaluate whether antipsychotic drugs can modulate the host epigenome and if so whether drug-induced epigenetic modulation can explain the heterogeneity in drug response.
Present study was conducted in in vitro cells and significance of these in vitro observations was further evaluated in a clinical setting, between drug responsive and nonresponsive schizophrenia patients. A number of DNA modifications were assessed at global level using 5-methylcytosine, 5-hydroxymethylcytosine and 5-formylcytosine followed by evaluating the expression of epigenetic modifier genes and their crosstalk with miRNAs.
In vitro data demonstrated that antipsychotic drugs induce epigenetic response by downregulating miRNA that target DNA methyltransferases, resulting in global hypermethylation. Similar trend was observed in clinical setting too and alterations were markedly associated with drug response rather than disease pathogenesis.
Study demonstrates that antipsychotic drugs can influence host methylome and thereby indicating its role in mediating a strong pharmacoepigenomic response.
本研究旨在评估抗精神病药物是否能调节宿主的表观基因组，如果可以，那么药物诱导的表观遗传修饰是否可以解释药物反应的异质性。
本研究在体外细胞中进行，并在临床环境中，在药物反应性和非反应性精神分裂症患者之间，进一步评估了这些体外观察结果的意义。使用 5-甲基胞嘧啶、5-羟甲基胞嘧啶和 5-甲酰胞嘧啶在全基因组水平上评估了许多 DNA 修饰，然后评估了表观遗传修饰基因的表达及其与 miRNAs 的相互作用。
体外数据表明，抗精神病药物通过下调靶向 DNA 甲基转移酶的 miRNA 诱导表观遗传反应，导致全基因组超甲基化。在临床环境中也观察到类似的趋势，这些改变与药物反应明显相关，而与疾病发病机制无关。
研究表明，抗精神病药物可以影响宿主甲基组，从而表明其在介导强烈的药物基因组反应中的作用。
