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Genetic contribution to lipid target achievement with statin therapy: a prospective study

The Pharmacogenomics Journal volume 20, pages 494–504 (2020)Cite this article

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Abstract

Statin therapy response is highly variable. Variants of lipid metabolism genes and statin pharmacokinetic modulators could play a role, however, the impact of most of these variants remains unconfirmed. A prospective and multicenter study included 252 patients was carried out in order to assess, according to achievement of LDL-C or non-HDL-C therapeutic targets and quantitative changes in lipid profiles, the impact of CETP, ABCA1, CYP2D6, and CYP2C9 gene candidate variants on the simvastatin, atorvastatin, and rosuvastatin response. Patients carrier ABCA1 rs2230806 and CYP2D6*3 variants are less likely to achieve therapeutic lipid targets (p = 0.020, OR = 0.59 [0.37, 0.93]; p = 0.040, OR = 0.23 [0.05, 0.93], respectively). Among CETP variants, rs708272 was linked to a 10.56% smaller reduction in LDL-C with rosuvastatin (95% CI = [1.27, 19.86] %; p = 0.028). In contrast, carriers of rs5882 had a 13.33% greater reduction in LDL-C (95% CI = [25.38, 1.28]; p = 0.032). If these findings are confirmed, ABCA1, CYP2D6, and CETP genotyping could be used to help predict which statin and dosage is appropriate in order to improve personalized medicine.

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Fig. 1: Achievement of LDL-C/non-HDL-C targets for all cases.

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Acknowledgements

We thank Arnald Alonso-Pastor, Emili Corbella-Inglés, Ferran Trias-Vilagut, Marta Fanlo- Maresma, Hannia Elena Lafuente-González, Xavier Jusmet, and Enric Juncadella-García who provided insight and expertize that greatly assisted the research. We also would like to thank to Mollet Hospital (FSM, Mollet del Vallès, Spain) for their unstiting support in this project. The present work was performed as part of the Biochemistry, Molecular Biology and Biomedicine doctoral program of Cristina Ruiz-Iruela at Universitat Autònoma de Barcelona (Barcelona, Spain).

Fundings

This research was supported by Fundació Parc Taulí Institut Universitari UAB (Parc Taulí recerca scholarship 2012, CSPT/CIR/2012) and Fundación José Luis Castaño (FENIN scholarship 2014, JLC/FENIN/2014) from the Spanish Society of Laboratory Medicine (SEQC).

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Authors and Affiliations

  1. Clinical Laboratory, IDIBELL-Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain

    Cristina Ruiz-Iruela, Beatriz Candás-Estébanez, Pedro Alía-Ramos & Ariadna Padró-Miquel

  2. phD student at Universitat Autònoma de Barcelona, Barcelona, Spain

    Cristina Ruiz-Iruela

  3. Cardiovascular Unit, IDIBELL-Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain

    Xavier Pintó-Sala

  4. Genetics Laboratory UDIAT-CD, Corporació Sanitària Parc Tauli, Sabadell, Barcelona, Spain

    Neus Baena-Díez

  5. Endocrinology Department, Corporació Sanitària Parc Taulí, Sabadell, Barcelona, Spain

    Assumpta Caixàs-Pedragós

  6. Hospitalet Clinical Laboratory, Centre Atenció Primària Just Oliveras, L’Hospitalet de Llobregat, Barcelona, Spain

    Roser Güell-Miró & Rosa Navarro-Badal

  7. Clinical Laboratory, Hospital Universitario Miguel Servet, Zaragoza, Spain

    Pilar Calmarza & Jose Luis Puzo-Foncilla

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  1. Cristina Ruiz-Iruela
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Ruiz-Iruela, C., Candás-Estébanez, B., Pintó-Sala, X. et al. Genetic contribution to lipid target achievement with statin therapy: a prospective study. Pharmacogenomics J 20, 494–504 (2020). https://doi.org/10.1038/s41397-019-0136-7

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