Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Curr Med Chem. 2018;25(24):2855-2871. doi: 10.2174/0929867324666170920145337.
Pharmacotranscriptomics aims to reach more accurate drug dosing based on interindividual transcriptome variations. Here, we provide an overview of RNA biomarkers that could predict the response to glucocorticoids (GCs), considered the standard for treatment of inflammatory bowel diseases (IBD), both in adult and pediatric patients. Although new biological agents are very effective in IBD treatment, GCs are still widely used for induction of remission in patients with moderate to severe disease. It is important to identify patients that are poor responders to GCs therapy, because suboptimal response is frequent and associated with various side effects. A number of genetic variants related to GC mechanism of action has been studied. However, the majority of reported associations are not consistent. In this regard, pharmacogenomic research is now exploring the world of RNAs. An appropriate regulation of the transcriptome, which mainly comprises mRNAs and non-coding RNAs that control gene expression, has a strong impact in the modulation of GC activity.
The aim of this review is to present the current knowledge of the role of the transcriptome in modulating GC response in pediatric IBD.
We will discuss the available literature, concerning the development of pharmacotranscriptomic biomarkers, focusing particularly on non-coding RNAs, and present the results in this field that elucidate a concrete benefit of translating the knowledge gained in the "omics" studies into clinical practice.
药物转录组学旨在根据个体转录组差异实现更精确的药物剂量。本文综述了 RNA 生物标志物在预测糖皮质激素（GC）反应中的作用，GC 是治疗炎症性肠病（IBD）的标准药物，在成人和儿科患者中均有应用。虽然新型生物制剂在 IBD 治疗中非常有效，但 GC 仍广泛用于诱导中重度疾病患者的缓解。识别 GC 治疗反应不佳的患者非常重要，因为这种情况很常见，且与多种副作用相关。已有大量与 GC 作用机制相关的遗传变异被研究，但大多数报道的关联并不一致。在这方面，药物基因组学研究正在探索 RNA 的世界。转录组的适当调节，主要包括控制基因表达的 mRNAs 和非编码 RNA，对 GC 活性的调节有很大影响。
本综述旨在介绍目前关于转录组在调节儿科 IBD 中 GC 反应中的作用的知识。
我们将讨论相关文献，涉及药物转录组学生物标志物的发展，特别关注非编码 RNA，并介绍该领域的研究结果，阐明将“组学”研究中获得的知识转化为临床实践的具体益处。
