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大麻素的药物遗传学

Pharmacogenetics of Cannabinoids.

作者信息

Hryhorowicz Szymon, Walczak Michal, Zakerska-Banaszak Oliwia, Słomski Ryszard, Skrzypczak-Zielińska Marzena

机构信息

Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32, 60-479, Poznan, Poland.

Department of Biochemistry and Biotechnology, University of Life Sciences, Dojazd 11, 60-632, Poznan, Poland.

出版信息

Eur J Drug Metab Pharmacokinet. 2018 Feb;43(1):1-12. doi: 10.1007/s13318-017-0416-z.

Abstract

Although the application of medical marijuana and cannabinoid drugs is controversial, it is a part of modern-day medicine. The list of diseases in which cannabinoids are promoted as a treatment is constantly expanding. Cases of significant improvement in patients with a very poor prognosis of glioma or epilepsy have already been described. However, the occurrence of side effects is still difficult to estimate, and the current knowledge of the therapeutic effects of cannabinoids is still insufficient. In our opinion, the answers to many questions and concerns regarding the medical use of cannabis can be provided by pharmacogenetics. Knowledge based on proteins and molecules involved in the transport, action, and metabolism of cannabinoids in the human organism leads us to predict candidate genes which variations are responsible for the presence of the therapeutic and side effects of medical marijuana and cannabinoid-based drugs. We can divide them into: receptor genes-CNR1, CNR2, TRPV1, and GPR55, transporters-ABCB1, ABCG2, SLC6A, biotransformation, biosynthesis, and bioactivation proteins encoded by CYP3A4, CYP2C19, CYP2C9, CYP2A6, CYP1A1, COMT, FAAH, COX2, ABHD6, ABHD12 genes, and also MAPK14. This review organizes the current knowledge in the context of cannabinoids pharmacogenetics according to individualized medicine and cannabinoid drugs therapy.

摘要

尽管医用大麻和大麻素药物的应用存在争议,但它仍是现代医学的一部分。大麻素被推荐用于治疗的疾病清单在不断扩大。已有文献报道,患有预后极差的胶质瘤或癫痫的患者病情有显著改善。然而,副作用的发生率仍难以估计,目前对大麻素治疗效果的了解仍不充分。我们认为,药物遗传学可以为许多关于大麻药用的问题和担忧提供答案。基于参与人体中大麻素运输、作用和代谢的蛋白质和分子的知识,使我们能够预测哪些基因变异与医用大麻和基于大麻素的药物的治疗效果和副作用有关。我们可以将它们分为:受体基因——CNR1、CNR2、TRPV1和GPR55,转运蛋白——ABCB1、ABCG2、SLC6A,由CYP3A4、CYP2C19、CYP2C9、CYP2A6、CYP1A1、COMT、FAAH、COX2、ABHD6、ABHD12基因以及MAPK14编码的生物转化、生物合成和生物激活蛋白。本综述根据个性化医疗和大麻素药物治疗,梳理了大麻素药物遗传学方面的现有知识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a71/5794848/f9f66bdf2634/13318_2017_416_Fig1_HTML.jpg

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