Swathy Babu, Saradalekshmi Koramannil R, Nair Indu V, Nair Chandrasekharan, Banerjee Moinak
Human Molecular Genetics Laboratory, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.
Mental Health Centre, Thiruvananthapuram, Kerala, India.
Epigenomics. 2017 Jun;9(6):811-821. doi: 10.2217/epi-2016-0181. Epub 2017 Apr 21.
It is imperative to differentiate the role of host epigenetics from pharmacoepigenetics in resolving therapeutic response. Therefore, the objective was to identify how antipsychotic drugs influence epigenetic response on pharmacogenes.
MATERIALS & METHODS: The study design was based on in vitro evaluation of pharmacoepigenetic response of haloperidol, clozapine and olanzapine. Post antipsychotic treatment, the alterations in expression of ABCB1, CYP1A2 and CYP3A4 were monitored, and followed up by promoter methylation and their target miRNA expression studies. Critical observations were followed up in a restrictive clinical setting.
Under in vitro conditions increased expression of ABCB1, CYP1A2 and CYP3A4 was observed which seems to be regulated by miR-27a and miR-128a and not by methylation. A similar pattern was observed in clinical setting with ABCB1, which was reflective of good therapeutic response.
The study demonstrates that antipsychotic drugs can influence miRNA-mediated epigenetic response in pharmacogenes resulting in modulating therapeutic response.
区分宿主表观遗传学与药物表观遗传学在解析治疗反应中的作用势在必行。因此，本研究的目的是确定抗精神病药物如何影响药物代谢基因的表观遗传反应。
本研究设计基于对氟哌啶醇、氯氮平和奥氮平的药物表观遗传反应的体外评估。抗精神病药物治疗后，监测ABCB1、CYP1A2和CYP3A4表达的变化，并通过启动子甲基化及其靶标miRNA表达研究进行随访。在严格的临床环境中对关键观察结果进行随访。
在体外条件下，观察到ABCB1、CYP1A2和CYP3A4的表达增加，这似乎受miR-27a和miR-128a调控，而非甲基化调控。在临床环境中，ABCB1也观察到类似模式，这反映了良好的治疗反应。
本研究表明，抗精神病药物可影响药物代谢基因中miRNA介导的表观遗传反应，从而调节治疗反应。
