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评估药物基因组学在人一生中的疗效。

Estimating the efficacy of pharmacogenomics over a lifetime.

作者信息

Ye Zhan, Mayer John, Leary Emili J, Kitchner Terrie, Dart Richard A, Brilliant Murray H, Hebbring Scott J

机构信息

Marshfield Clinic Research Institute, Marshfield, WI, United States.

出版信息

Front Med (Lausanne). 2023 Oct 31;10:1006743. doi: 10.3389/fmed.2023.1006743. eCollection 2023.

Abstract

It is well known that common variants in specific genes influence drug metabolism and response, but it is currently unknown what fraction of patients are given prescriptions over a lifetime that could be contraindicated by their pharmacogenomic profiles. To determine the clinical utility of pharmacogenomics over a lifetime in a general patient population, we sequenced the genomes of 300 deceased Marshfield Clinic patients linked to lifelong medical records. Genetic variants in 33 pharmacogenes were evaluated for their lifetime impact on drug prescribing using extensive electronic health records. Results show that 93% of the 300 deceased patients carried clinically relevant variants. Nearly 80% were prescribed approximately three medications on average that may have been impacted by these variants. Longitudinal data suggested that the optimal age for pharmacogenomic testing was prior to age 50, but the optimal age is greatly influenced by the stability of the population in the healthcare system. This study emphasizes the broad clinical impact of pharmacogenomic testing over a lifetime and demonstrates the potential application of genomic medicine in a general patient population for the advancement of precision medicine.

摘要

众所周知,特定基因中的常见变异会影响药物代谢和反应,但目前尚不清楚在一生中,有多大比例的患者所开具的处方会因其药物基因组特征而存在禁忌。为了确定药物基因组学在普通患者群体一生中的临床效用,我们对300名与终身医疗记录相关的已故马什菲尔德诊所患者的基因组进行了测序。利用广泛的电子健康记录,评估了33个药物基因中的遗传变异对其一生药物处方的影响。结果显示,300名已故患者中有93%携带临床相关变异。近80%的患者平均开具了约三种可能受这些变异影响的药物。纵向数据表明,药物基因组检测的最佳年龄是在50岁之前,但最佳年龄受医疗系统中人群稳定性的影响很大。这项研究强调了药物基因组检测在一生中的广泛临床影响,并证明了基因组医学在普通患者群体中对推进精准医学的潜在应用。

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