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Pharmacogenetics of Lipid-Lowering Agents: an Update Review on Genotype-Dependent Effects of HDL-Targetingand Statin Therapies

  • Genetics and Genomics (A. Marian, Section Editor)
  • Published:
Current Atherosclerosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

High-density lipoproteins (HDL) are involved in reverse cholesterol transport. Results from randomized trials of HDL-targeting therapies, including cholesteryl ester transfer protein (CETP) inhibitors, have shown a lack of benefit in unsegmented populations. These observations could be explained by inter-individual variability of clinical responses to such agents depending on the patients’ genotypes. In parallel, although lowering of LDL cholesterol (LDL-c) with statin therapy reduces the risk of vascular events in a wide range of individuals, inter-individual variability exists with regard to LDL-c-lowering response as well as efficacy in reducing major cardiovascular events.

Recent Findings

Pharmacogenomic analyses were performed in the dal-OUTCOMES and dal-PLAQUE-2 studies. Beneficial and concordant results were observed in patients with the favorable genotype when treated with the CETP inhibitor dalcetrapib. Similarly, previous studies revealed genetic variants associated with differential LDL-c response to statin therapy.

Summary

In this review, we discuss the pharmacogenetic determinants of HDL-targeting and statin therapy responses in light of the latest available published data, and their potential therapeutic applications.

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Author information

Authors and Affiliations

  1. Department of Medicine, Montreal Heart Institute, 5000 Belanger St, Montreal, Quebec, H1T 1C8, Canada

    Nathan Messas, Marie-Pierre Dubé & Jean-Claude Tardif

  2. Pôle d’Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Strasbourg, France

    Nathan Messas

  3. Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada

    Marie-Pierre Dubé & Jean-Claude Tardif

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  1. Nathan Messas
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Corresponding author

Correspondence to Jean-Claude Tardif.

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Conflict of Interest

Dr. Nathan Messas has received financial support (Fellowship grants) from Abbott Vascular France, Biotronik France, and Biosensors France. Dr. Tardif has received research support from Amarin, AstraZeneca, DalCor, Esperion, Ionis, Merck, Pfizer, Sanofi, and Servier; honoraria from DalCor, Pfizer, Sanofi, and Servier, and holds minor equity interest in DalCor. He is mentioned as an author of a pending patent on pharmacogenomics-guided CETP inhibition. Dr. Dubé has received research support from AstraZeneca, DalCor, and Servier; honoraria from DalCor, holds minor equity interest in DalCor and holds stocks in Xenon. She is mentioned as an author of a pending patent on pharmacogenomics-guided CETP inhibition.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Genetics and Genomics

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Messas, N., Dubé, MP. & Tardif, JC. Pharmacogenetics of Lipid-Lowering Agents: an Update Review on Genotype-Dependent Effects of HDL-Targetingand Statin Therapies. Curr Atheroscler Rep 19, 43 (2017). https://doi.org/10.1007/s11883-017-0679-5

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  • DOI: https://doi.org/10.1007/s11883-017-0679-5

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