Cung Michele, Loftus John, Marzinke Mark A, Stevenson James M
Department of Pharmacy, Johns Hopkins Hospital, Baltimore, MD, USA.
Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Pharmacogenomics. 2025 Jan-Feb;26(1-2):1-7. doi: 10.1080/14622416.2025.2479409. Epub 2025 Mar 20.
Providers can use combinatorial pharmacogenomic panels to aid psychiatric medication prescribing. Results are typically documented in static documents which list the genotype and predicted phenotype (interpretation). However, genotype-to-phenotype translations can differ between laboratories and change as scientific consensuses evolves. Here, we describe the implications of reinterpreting phenotype after combinatorial psychiatric pharmacogenomic testing in a real-world setting.
143 patients underwent testing from 2014 to 2021. Reported genotypes and phenotypes were compared to 2024 Clinical Pharmacogenetics Implementation Consortium definitions. Chi-square tests and logistic regression were used to examine the differences in phenotype frequencies before and after reinterpretation and examine the association with time since testing.
Eighty-one patients (57%) required at least one updated interpretation. CYP2C19 interpretations changed for 44/143 patients (31%), followed by CYP2D6 (29%), CYP2B6 (3%), and CYP2C9 (1%). Reinterpretation reduced the number of CYP2D6 ultrarapid and poor metabolizers ( = 0.005), which has implications for antidepressant prescribing. Likelihood of a patient having a reinterpreted phenotype was not associated with time since reporting ( = 0.71).
Reported phenotypes from combinatorial PGx testing often do not align with current standardized definitions, even from tests performed recently. Health systems should establish procedures to standardize and periodically update pharmacogenomic interpretations.
医疗服务提供者可使用组合式药物基因组学检测板来辅助精神科药物处方。结果通常记录在静态文档中，这些文档列出了基因型和预测的表型（解读）。然而，不同实验室之间基因型到表型的转化可能存在差异，并且会随着科学共识的发展而变化。在此，我们描述了在现实环境中对组合式精神科药物基因组学检测后的表型进行重新解读的影响。
2014年至2021年期间，143名患者接受了检测。将报告的基因型和表型与2024年临床药物遗传学实施联盟的定义进行比较。使用卡方检验和逻辑回归来检查重新解读前后表型频率的差异，并检查与检测后时间的关联。
81名患者（57%）至少需要一次更新解读。44/143名患者（31%）的CYP2C19解读发生了变化，其次是CYP2D6（29%）、CYP2B6（3%）和CYP2C9（1%）。重新解读减少了CYP2D6超快代谢者和弱代谢者的数量（=0.005），这对抗抑郁药的处方有影响。患者出现重新解读表型的可能性与报告后的时间无关（=0.71）。
组合式药物基因组学检测报告的表型通常与当前的标准化定义不一致，即使是最近进行的检测也是如此。卫生系统应建立程序，以规范和定期更新药物基因组学解读。
