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Combining familial hypercholesterolemia and statin genetic studies as a strategy for the implementation of pharmacogenomics. A multidisciplinary approach

The Pharmacogenomics Journal volume 22, pages 180–187 (2022)Cite this article

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Abstract

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.

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Fig. 1
Fig. 2: Decision tree for statin genotype-based prescription.
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Data availability

The data used in the analysis of this study is available from the corresponding author on upon request.

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Authors and Affiliations

  1. Health in Code S.L., Scientific Department, A Coruña, Spain

    Luis Ramudo-Cela, Sara Santana-Martínez, Maite García-Ramos, Mariano Bergamino, Diego García-Giustiniani, Martín Ortíz & Lorenzo Monserrat-Iglesias

  2. Complexo Hospitalario Universitario A Coruña, A Coruña, Spain

    Luis Ramudo-Cela

  3. Universidade da Coruña, A Coruña, Spain

    Luis Ramudo-Cela

  4. Health in Code S.L., Laboratory Department, A Coruña, Spain

    Paula Vélez-Vieitez & Luis Santomé-Collazo

  5. Department of Internal Medicine, Hospital Universitario Marqués de Valdecilla-IDIVAL, University of Cantabria, Santander, Spain

    Jose Luis Hernández-Hernández & Carmen García-Ibarbia

  6. Servicio de Medicina Interna, Hospital Virgen de las Nieves, Granada, España

    Pablo González-Bustos

  7. Department of Cardiology, Hospital Regional Universitario de Málaga, Málaga, Spain

    Patricia Ruíz-Martín & Jaime González-Lozano

  8. Health in Code S.L., Bioinformatics Department, A Coruña, Spain

    Andrea Grana-Fernandez & Pablo Cabaleiro-Cerviño

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  1. Luis Ramudo-Cela
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Contributions

LR—originated the research, wrote, reviewed, and edited manuscript. SS, MG, MG, PV, JLS, AG, PC screened records, extracted data, analyzed data, wrote original draft. JLH, CG, PG, PR, JG reviewed and edited the manuscript. DG, MO, LM supervised the project, verified data, interpreted results, reviewed, and edited the manuscript. All authors were involved in drafting the manuscript. All authors approved the final version of the manuscript for submission and agree to be accountable for the information provided in the manuscript

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Correspondence to Luis Ramudo-Cela.

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Competing interests

LRC, SSM, MGR, MB, DGG, PVV, LSC, AGF, PCC are employees of Health in Code SL. LMI receives personal fees from Health in Code SL.

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Ramudo-Cela, L., Santana-Martínez, S., García-Ramos, M. et al. Combining familial hypercholesterolemia and statin genetic studies as a strategy for the implementation of pharmacogenomics. A multidisciplinary approach. Pharmacogenomics J 22, 180–187 (2022). https://doi.org/10.1038/s41397-022-00274-8

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