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Exploration of interethnic variation in the ibuprofen metabolizing enzyme CYP2C9: a genetic-based cautionary guide for treatment of COVID-19 symptoms
medRxiv - Genetic and Genomic Medicine Pub Date : 2021-03-09 , DOI: 10.1101/2021.01.09.21249508
Ammar Ali Almarzooq

Coronavirus disease 2019 (COVID-19), is a rapidly spreading infectious illness that causes a debilitating respiratory syndrome. While non-steroidal anti-inflammatory drugs (NSAIDs), may be prescribed for the management of pain and fever, there was early controversy on the use of ibuprofen for symptomatic treatment of COVID-19. P450 enzyme CYP2C9 are known to be involved in the metabolism of NSAIDs. Although no study has been conducted in the setting of population genetics in patients with COVID-19 yet, there are plausible mechanisms by which genetic determinants may play a role in adverse drug reactions (ADRs). In this work, we adjusted expected phenotype frequencies based on racial demographic models dependent on population ancestry in drug responses and toxicity events associated with ibuprofen treatment. A cohort of 101 Jordanian Arab samples retrospectively were selected and genotyped using Affymetrix DMET Plus Premier Package, within the context of over 100,000 global subjects in 417 published reports. European populations are 7.2x more likely to show impaired ibuprofen metabolism than Sub-Saharan populations, and 4.5x more likely than East Asian ancestry populations. Hence, a proactive assessment of the most likely gene-drug candidates will lead to more effective treatments and a better understanding of the role of pharmacogenetics for COVID-19.

中文翻译:

探索布洛芬代谢酶CYP2C9中的种族间差异:基于遗传的COVID-19症状警告指南

冠状病毒病2019(COVID-19)是一种迅速传播的传染病,可导致呼吸衰竭综合症。虽然可以使用非甾体类抗炎药(NSAIDs)治疗疼痛和发烧,但布洛芬用于对症治疗COVID-19尚有争议。已知P450酶CYP2C9参与NSAID的代谢。尽管尚未对COVID-19患者的群体遗传学设置进行任何研究,但仍有一些合理的机制可以通过遗传决定因素在药物不良反应(ADR)中发挥作用。在这项工作中,我们根据种族人口模型调整了预期的表型频率,而人口统计学模型取决于布洛芬治疗相关的药物反应和毒性事件中的人群祖先。在417个已发表的报告中,在全球100,000多个研究对象的背景下,使用Affymetrix DMET Plus Premier Package回顾性筛选了101个约旦阿拉伯样本,并对它们进行基因分型。与撒哈拉以南地区相比,欧洲人口布洛芬代谢受损的可能性高7.2倍,比东亚血统人口高4.5倍。因此,对最可能的基因药物候选者的积极评估将导致更有效的治疗,并更好地理解药物遗传学对COVID-19的作用。是东亚血统人口的5倍。因此,对最有可能的基因药物候选者的积极评估将导致更有效的治疗,并更好地理解药物遗传学对COVID-19的作用。是东亚血统人口的5倍。因此,对最可能的基因药物候选者的积极评估将导致更有效的治疗,并更好地理解药物遗传学对COVID-19的作用。
更新日期:2021-03-09
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