Precision Medicine Unit, Biomedical Data Science Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Division of Internal Medicine, Department of Medicine, University of Lausanne and University Hospital of Lausanne, Lausanne, Switzerland.
Clin Transl Sci. 2024 Sep;17(9):e70009. doi: 10.1111/cts.70009.
Drug type and dosing recommendation have been designed and optimized based on average response in the general population. Yet, there is significant inter-individual variability in drug response, which results in treatment inefficacy or adverse drug reactions in a subset of patients. This is partly due to genetic factors that typically affect drug metabolism or clearance. To verify the relevance and applicability of international pharmacogenetic guidelines in the Swiss population, we genotyped 1533 patients from a hospital-based biobank who received at least 30 different drugs, as documented in their electronic health record. We then assessed the prevalence of clinically actionable variants in 13 high-risk pharmacogenes. We compared the allele frequencies obtained in the hospital-based cohort with those of a Swiss population-based cohort of 4791 individuals. The prevalence of clinically actionable variants was comparable between the two cohorts, with most study participants (97.3%) carrying at least one actionable pharmacogenetic variant. We then assessed the frequency of high-risk prescriptions due to actionable gene-drug interactions and observed that 31% of patients in the hospital-based cohort were prescribed at least one drug for which they carried a high-risk variant, and for which international guidelines recommend a change of drug or dosage. Our analysis confirms the high prevalence of actionable pharmacogenetic variants in the Swiss population. It also shows that a substantial minority of patients are exposed to drugs for which they carry potentially problematic variants. Implementing a genetically informed approach to drug prescribing could have a positive impact on the quality of healthcare delivery.
药物类型和剂量推荐是基于一般人群的平均反应设计和优化的。然而，药物反应在个体之间存在显著的变异性，这导致一部分患者的治疗无效或出现药物不良反应。这部分是由于遗传因素，这些因素通常会影响药物代谢或清除。为了验证国际药物遗传学指南在瑞士人群中的相关性和适用性，我们对一个基于医院的生物库中的 1533 名患者进行了基因分型，这些患者在电子健康记录中至少接受了 30 种不同的药物治疗。然后，我们评估了 13 个高风险药物基因中临床可操作变异体的患病率。我们将基于医院的队列中的等位基因频率与 4791 名瑞士人群队列中的频率进行了比较。两个队列中的临床可操作变异体的患病率相当，大多数研究参与者（97.3%）携带至少一个可操作的药物遗传学变异体。然后，我们评估了由于可操作的基因-药物相互作用而导致的高危处方的频率，观察到基于医院的队列中有 31%的患者至少开了一种他们携带高风险变异体的药物，而国际指南建议改变药物或剂量。我们的分析证实了瑞士人群中可操作的药物遗传学变异体的高患病率。它还表明，相当一部分患者接触到了他们可能存在问题的变异体的药物。实施基于遗传信息的药物处方方法可能对医疗保健的质量产生积极影响。
