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CYP - GUIDES数据的亚组分析:评估不同种族抑郁症患者队列中药物 - 基因相互作用的发生率及影响

Sub-Analysis of CYP-GUIDES Data: Assessing the Prevalence and Impact of Drug-Gene Interactions in an Ethnically Diverse Cohort of Depressed Individuals.

作者信息

Crutchley Rustin D, Keuler Nicole

机构信息

Department of Pharmacotherapy, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Yakima, WA, United States.

School of Pharmacy, University of the Western Cape, Cape Town, South Africa.

出版信息

Front Pharmacol. 2022 Apr 12;13:884213. doi: 10.3389/fphar.2022.884213. eCollection 2022.

Abstract

Minority groups are underrepresented in pharmacogenomics (PGx) research. Recent sub-analysis of CYP-GUIDES showed reduced length of stay (LOS) in depressed patients with CYP2D6 sub-functional status. Our primary objective was to determine whether PGx guided (G) versus standard treatment (S) influenced LOS among different race/ethnic groups. Secondary objectives included prevalence of drug-gene interactions (DGIs) and readmission rates (RAR). Retrospective sub-analysis of CYP-GUIDES data comprising CYP2D6 phenotypes was reclassified using standardized CYP2D6 genotype to phenotype recommendations from the Clinical Pharmacogenetics Implementation Consortium (CPIC) and Dutch Pharmacogenetics Working Group (DPWG). The Mann-Whitney test was used to determine differences in LOS between groups G and S and Kruskal Wallis test to compare LOS among different race/ethnic groups. Logistic regression was used to determine covariates associated with RAR. This study included 1,459 patients with 67.3% in G group ( = 982). The majority of patients were White (57.5%), followed by Latinos (25.6%) and Blacks (12.3%). Although there were no differences in LOS between G and S groups, Latinos had significant shorter LOS than Whites ( = 0.002). LOS was significantly reduced by 5.6 days in poor metabolizers in group G compared to S ( = 0.002). The proportion of supra functional and ultra-rapid metabolizers (UMs) were 6 and 20.3% using CYP-GUIDES and CPIC/DPWG definitions, respectively. Prevalence of DGIs was 40% with significantly fewer DGIs in Blacks ( < 0.001). Race/ethnicity was significantly associated with RAR (aOR 1.30; = 0.003). A greater number of patients were classified as CYP2D6 UMs using CPIC/DPWG definitions as compared to CYP-GUIDES definitions. This finding may have clinical implications for using psychotropics metabolized by CYP2D6.

摘要

少数群体在药物基因组学(PGx)研究中的代表性不足。最近对CYP - GUIDES的亚分析显示,CYP2D6亚功能状态的抑郁症患者住院时间(LOS)缩短。我们的主要目标是确定PGx指导治疗(G)与标准治疗(S)对不同种族/族裔群体的住院时间是否有影响。次要目标包括药物 - 基因相互作用(DGI)的患病率和再入院率(RAR)。对包含CYP2D6表型的CYP - GUIDES数据进行回顾性亚分析,使用临床药物基因组学实施联盟(CPIC)和荷兰药物基因组学工作组(DPWG)的标准化CYP2D6基因型到表型的建议进行重新分类。使用Mann - Whitney检验确定G组和S组之间住院时间的差异,使用Kruskal Wallis检验比较不同种族/族裔群体之间的住院时间。使用逻辑回归确定与再入院率相关的协变量。本研究纳入了1459例患者,其中G组占67.3%(n = 982)。大多数患者为白人(57.5%),其次是拉丁裔(25.6%)和黑人(12.3%)。虽然G组和S组之间的住院时间没有差异,但拉丁裔的住院时间明显短于白人(P = 0.002)。与S组相比,G组中代谢不良者的住院时间显著缩短了5.6天(P = 0.002)。使用CYP - GUIDES和CPIC/DPWG定义时,超功能和超快代谢者(UMs)的比例分别为6%和20.3%。DGI的患病率为40%,黑人中的DGI明显较少(P < 0.001)。种族/族裔与再入院率显著相关(调整后的比值比1.30;P = 0.003)。与CYP - GUIDES定义相比,使用CPIC/DPWG定义时,更多患者被归类为CYP2D6 UMs。这一发现可能对使用由CYP2D6代谢的精神药物具有临床意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee13/9039251/2ee6ebdb3a8f/fphar-13-884213-g001.jpg

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