Magarbeh Leen, Gorbovskaya Ilona, Wells Richard, Jhirad Reuven, Le Foll Bernard, Müller Daniel J
Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada.
J Pers Med. 2023 May 30;13(6):918. doi: 10.3390/jpm13060918.
There has been a worldwide substantial increase in accidental opioid-overdose deaths. The aim of this review, along with preliminary results from our pilot study, is to highlight the use of pharmacogenetics as a tool to predict causes of accidental opioid-overdose death. For this review, a systematic literature search of PubMed between the time period of January 2000 to March 2023 was carried out. We included study cohorts, case-controls, or case reports that investigated the frequency of genetic variants in opioid-related post-mortem samples and the association between these variants and opioid plasma concentrations. A total of 18 studies were included in our systematic review. The systematic review provides evidence of the use of , and to a lower extent, and genotyping in identifying unexpectedly high or low opioid and metabolite blood concentrations from post-mortem samples. Our own pilot study provides support for an enrichment of the *4-allele in our methadone-overdose sample ( = 41) compared to the anticipated frequency in the general population. The results from our systematic review and the pilot study highlight the potential of pharmacogenetics in determining vulnerability to overdose of opioids.
全球意外阿片类药物过量死亡人数大幅增加。本综述的目的以及我们初步研究的结果，是强调药物遗传学作为预测意外阿片类药物过量死亡原因的工具的应用。在本次综述中，我们对2000年1月至2023年3月期间的PubMed进行了系统的文献检索。我们纳入了研究队列、病例对照或病例报告，这些研究调查了阿片类药物相关尸检样本中基因变异的频率，以及这些变异与阿片类药物血浆浓度之间的关联。我们的系统综述共纳入了18项研究。该系统综述提供了证据，证明在一定程度上利用[具体基因]、[具体基因]和[具体基因]基因分型来识别尸检样本中意外高或低的阿片类药物和代谢物血药浓度。我们自己的初步研究支持，与普通人群的预期频率相比，我们的美沙酮过量样本（n = 41）中*4等位基因富集。我们系统综述和初步研究的结果突出了药物遗传学在确定阿片类药物过量易感性方面的潜力。
