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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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).
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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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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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DOI: https://doi.org/10.1038/s41397-019-0136-7