Saunders David, Hellwig Lydia D, Pagani Austin, De Castro Mauricio, Haigney Mark, Poon Lucas, Ehat Nate, Heroy Andrew, Libbus Joya, Fox Keiko, Kalra Sachi, Arnold Thomas B, Turner Clesson, Black John Logan, Scherer Steven E, Moyer Ann M
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Pharmacogenomics. 2024;25(16-18):637-645. doi: 10.1080/14622416.2025.2466413. Epub 2025 Feb 21.
Pharmacogenetic (PGx) screening is intended to optimize drug efficacy and reduce adverse drug reactions. Current screening options include genotyping assays for preselected PGx variants and broader next-generation sequencing panels (NGS). Few studies have directly compared preemptive PGx screening methods.
The two PGx methods were compared in a cross-sectional study of adult Military Health System (MHS) clinic beneficiaries. Participants had initial targeted CYP2C19/CYP2D6 genotyping at a Military Health System Laboratory. Genotyping was followed by multi-gene NGS testing. Current prescriptions were recorded and potential drug-drug interactions screened to evaluate prescribing risk.
All participants (100%) had at least one clinically actionable NGS panel result compared to 81% with targeted CYP2C19/CYP2D6 genotyping. Participants ( = 162) had an average of 6.6 (range 0-22) prescriptions and 2.7 (range 0-24) drug-drug interactions. Among those with at least one clinically actionable NGS result, 42% were currently taking medication with actionable CPIC guidelines (Level A/B), compared with 24% with CYP2C19/CYP2D6 genotyping. Sixteen participants (10%) had uncertain NGS panel results, with none for CYP2C19/CYP2D6 genotyping.
Preemptive multi-gene NGS detected more clinically actionable PGx results than targeted genotyping. Effective PGx screening in the MHS may decrease preventable adverse effects and improve military readiness.
药物遗传学(PGx)筛查旨在优化药物疗效并减少药物不良反应。当前的筛查选项包括针对预先选定的PGx变异体的基因分型检测以及更广泛的下一代测序面板(NGS)。很少有研究直接比较过先发制人的PGx筛查方法。
在一项针对成年军事卫生系统(MHS)诊所受益人的横断面研究中比较了两种PGx方法。参与者在军事卫生系统实验室进行了初始的靶向CYP2C19/CYP2D6基因分型。基因分型之后进行了多基因NGS检测。记录当前处方并筛查潜在的药物相互作用以评估处方风险。
所有参与者(100%)至少有一项具有临床可操作性的NGS面板结果,而靶向CYP2C19/CYP2D6基因分型的这一比例为81%。参与者(n = 162)平均有6.6(范围0 - 22)张处方和2.7(范围0 - 24)种药物相互作用。在那些至少有一项具有临床可操作性的NGS结果的参与者中,42%目前正在服用符合可操作的临床药物基因组学实施联盟(CPIC)指南(A/B级)的药物,而CYP2C19/CYP2D6基因分型的这一比例为24%。16名参与者(10%)的NGS面板结果不确定,而CYP2C19/CYP2D6基因分型没有不确定结果。
先发制人的多基因NGS检测到的具有临床可操作性的PGx结果比靶向基因分型更多。在MHS中进行有效的PGx筛查可能会减少可预防的不良反应并提高军事准备状态。