Habtemariam Henok D, Guchelaar Henk-Jan
Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
Pharmaceuticals (Basel). 2022 Feb 19;15(2):252. doi: 10.3390/ph15020252.
Pharmacogenomics (PGx) entails the study of heritability of drug response. This may include both variability in genes related to pharmacokinetics (drug absorption, distribution, metabolism and excretion) and pharmacodynamics (e.g., drug receptors or signaling pathways). Individualizing drug therapy taking into account the genetic profile of the patient has the potential to make drug therapy safer and more effective. Currently, this approach relies on the determination of genetic variants in pharmacogenes by genotyping. However, it is widely acknowledged that large variability in gene expression is attributed to non-structural genetic variants. Therefore, at least from a theoretical viewpoint individualizing drug therapy based upon expression of pharmacogenes rather than on genotype may be advantageous but has been difficult to implement in the clinical setting. Extracellular vesicles (EVs) are lipid encapsulated structures that contain cargo such as lipids, nucleic acids and proteins. Since their cargo is tissue- and cell-specific they can be used to determine the expression of pharmacogenes in the liver. In this review, we describe methods of EV isolation and the potential of EVs isolated from liquid biopsies as a tool to determine the expression of pharmacogenes for use in personalized medicine.
药物基因组学(PGx)涉及对药物反应遗传性的研究。这可能包括与药代动力学(药物吸收、分布、代谢和排泄)以及药效学(例如,药物受体或信号通路)相关基因的变异性。考虑患者的基因特征来实现药物治疗个体化,有可能使药物治疗更安全、更有效。目前,这种方法依赖于通过基因分型来确定药物代谢基因中的遗传变异。然而,人们普遍认识到基因表达的巨大变异性归因于非结构遗传变异。因此,至少从理论观点来看,基于药物代谢基因的表达而非基因型来实现药物治疗个体化可能具有优势,但在临床环境中却难以实施。细胞外囊泡(EVs)是脂质包裹的结构,包含脂质、核酸和蛋白质等物质。由于其内容物具有组织和细胞特异性,它们可用于确定肝脏中药物代谢基因的表达。在本综述中,我们描述了EVs的分离方法以及从液体活检中分离的EVs作为一种工具来确定药物代谢基因表达以用于个性化医疗的潜力。