The diagnostic process of familial hypercholesterolemia frequently involves the use of genetic studies. Patients are treated with lipid-lowering drugs, frequently statins. Although pharmacogenomic clinical practice guidelines focusing on genotype-based statin prescription have been published, their use in routine clinical practice remains very modest.

We have implemented a new NGS strategy that combines a panel of genes related to familial hypercholesterolemia with genomic regions related to the pharmacogenomics of lipid-lowering drugs described in clinical practice guidelines and in EMA and FDA drug labels. A multidisciplinary team of doctors, biologists, and pharmacists creates a clinical report that provides diagnostic and therapeutic findings using a knowledge management and clinical decision support system, as well as an algorithm for treatment selection.

For 12 months, a total of 483 genetic diagnostic studies for familial hypercholesterolemia were carried out, of which 221 (45.8%) requested a complementary pharmacogenomic test. Of these 221 patients, 66.5% were carriers of actionable variants in any of the studied pharmacogenomic pathways: 46.6% of patients in one pathway, 19.0% in two pathways, and 0.9% in three pathways. 45.7% of patients could have a response to atorvastatin different from that of the reference population, 45.7% for simvastatin and lovastatin, 29.0% for fluvastatin, and 6.7% patients for pitavastatin.

This implementation approach facilitates the incorporation of pharmacogenomic studies in clinical care practice, it does not add complexity nor additional steps to laboratory processes, and improves the pharmacotherapeutic process of patients.

家族性高胆固醇血症的诊断过程经常涉及使用基因研究。患者接受降脂药物治疗，通常是他汀类药物。尽管已经发表了侧重于基于基因型的他汀类药物处方的药物基因组临床实践指南，但它们在常规临床实践中的应用仍然非常有限。

我们实施了一项新的 NGS 策略，将一组与家族性高胆固醇血症相关的基因与与临床实践指南以及 EMA 和 FDA 药物标签中描述的降脂药物的药物基因组学相关的基因组区域相结合。一个由医生、生物学家和药剂师组成的多学科团队创建一份临床报告，该报告使用知识管理和临床决策支持系统以及治疗选择算法提供诊断和治疗结果。

在 12 个月内，共进行了 483 项家族性高胆固醇血症的基因诊断研究，其中 221 项（45.8%）要求进行补充药物基因组学测试。在这 221 名患者中，66.5% 是任何研究药物基因组途径中可操作变异的携带者：46.6% 的患者在一个途径中，19.0% 在两个途径中，0.9% 在三个途径中。45.7% 的患者对阿托伐他汀的反应可能与参考人群不同，辛伐他汀和洛伐他汀为 45.7%，氟伐他汀为 29.0%，匹伐他汀为 6.7%。

这种实施方法有助于将药物基因组学研究纳入临床护理实践，它不会增加实验室过程的复杂性或额外步骤，并改善患者的药物治疗过程。