Sayer Michael, Duche Ashley, Nguyen Trang Jenny Tran, Le Michelle, Patel Kunj, Vu Jacqueline, Pham Danny, Vernick Brianne, Beuttler Richard, Roosan Don, Roosan Moom R
Department of Pharmacy Practice, Chapman University School of Pharmacy, Irvine, CA, United States.
College of Pharmacy, Western University of Health Sciences, Pomona, CA, United States.
Front Genet. 2021 Sep 28;12:719671. doi: 10.3389/fgene.2021.719671. eCollection 2021.
Despite the potential to improve patient outcomes, the application of pharmacogenomics (PGx) is yet to be routine. A growing number of PGx implementers are leaning toward using combinatorial PGx (CPGx) tests (i.e., multigene tests) that are reusable over patients' lifetimes. However, selecting a single best available CPGx test is challenging owing to many patient- and population-specific factors, including variant frequency differences across ethnic groups. The primary objective of this study was to evaluate the detection rate of currently available CPGx tests based on the cytochrome P450 (CYP) gene variants they target. The detection rate was defined as the percentage of a given population with an "altered metabolizer" genotype predicted phenotype, where a CPGx test targeted both gene variants a prospective diplotypes. A potential genotype predicted phenotype was considered an altered metabolizer when it resulted in medication therapy modification based on Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. Targeted variant CPGx tests found in the Genetic Testing Registry (GTR), gene selection information, and diplotype frequency data from the Pharmacogenomics Knowledge Base (PharmGKB) were used to determine the detection rate of each CPGx test. Our results indicated that the detection rate of CPGx tests covering CYP2C19, CYP2C9, CYP2D6, and CYP2B6 show significant variation across ethnic groups. Specifically, the Sub-Saharan Africans have 63.9% and 77.9% average detection rates for CYP2B6 and CYP2C19 assays analyzed, respectively. In addition, East Asians (EAs) have an average detection rate of 55.1% for CYP2C9 assays. Therefore, the patient's ethnic background should be carefully considered in selecting CPGx tests.
尽管药物基因组学（PGx）有改善患者治疗效果的潜力，但其应用尚未成为常规操作。越来越多的PGx实施者倾向于使用可在患者一生中重复使用的组合PGx（CPGx）检测（即多基因检测）。然而，由于许多患者和人群特有的因素，包括不同种族间的变异频率差异，选择单一最佳可用的CPGx检测具有挑战性。本研究的主要目的是评估基于其靶向的细胞色素P450（CYP）基因变异的现有CPGx检测的检出率。检出率定义为具有“代谢改变者”基因型预测表型的给定人群的百分比，其中CPGx检测针对两种基因变异和预期的双倍型。当潜在的基因型预测表型根据临床药物基因组学实施联盟（CPIC）指南导致药物治疗调整时，该表型被视为代谢改变者。利用基因检测注册库（GTR）中发现的靶向变异CPGx检测、基因选择信息以及药物基因组学知识库（PharmGKB）中的双倍型频率数据来确定每种CPGx检测的检出率。我们的结果表明，涵盖CYP2C19、CYP2C9、CYP2D6和CYP2B6的CPGx检测的检出率在不同种族间存在显著差异。具体而言，撒哈拉以南非洲人分析的CYP2B6和CYP2C19检测的平均检出率分别为63.9%和77.9%。此外，东亚人（EA）的CYP2C9检测平均检出率为55.1%。因此，在选择CPGx检测时应仔细考虑患者的种族背景。
