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Genetics of Cholesterol Efflux

  • Genetics (AJ Marian, Section Editor)
  • Published:
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Abstract

Plasma levels of high-density lipoprotein cholesterol (HDL-C) show an inverse association with coronary heart disease (CHD). As a biological trait, HDL-C is strongly genetically determined, with a heritability index ranging from 40 % to 60 %. HDL represents an appealing therapeutic target due to its beneficial pleiotropic effects in preventing CHD. This review focuses on the genetic basis of cellular cholesterol efflux, the rate-limiting step in HDL biogenesis. There are several monogenic disorders (e.g., Tangier disease, caused by mutations within ABCA1) affecting HDL biogenesis. Importantly, many disorders of cellular cholesterol homeostasis cause a reduced HDL-C. We integrate information from family studies and linkage analyses with that derived from genome-wide association studies (GWAS) and review the recent identification of micro-RNAs (miRNA) involved in cellular cholesterol metabolism. The identification of genomic pathways related to HDL may help pave the way for novel therapeutic approaches to promote cellular cholesterol efflux as a therapeutic modality to prevent atherosclerosis.

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Authors and Affiliations

  1. Cardiovascular Research Laboratories, Division of Cardiology, Department of Biochemistry, Faculty of Medicine, McGill University and McGill University Health Center / Royal Victoria Hospital, 687 Pine Avenue West, Montreal, QC, H3A 1A1, Canada

    Iulia Iatan

  2. Magistère Européen de Génétique, Université Paris Diderot - Paris 7, 5 Thomas Mann street, 775013, Paris, France

    Aurélien Palmyre

  3. Cardiovascular Research Laboratories, Division of Cardiology, Department of Human Genetics, Faculty of Medicine, McGill University and McGill University Health Center / Royal Victoria Hospital, 687 Pine Avenue West, Montreal, QC, H3A 1A1, Canada

    Sarah Alrasheed

  4. Cardiovascular Research Laboratories, Division of Cardiology, McGill University Health Centre / Royal Victoria Hospital, 687 Pine Avenue West, Montreal, QC, H3A 1A1, Canada

    Isabelle Ruel

  5. Faculty of Medicine, Novartis Chair in Medicine, Cardiovascular Research Laboratories, Division of Cardiology, McGill University and McGill University Health Center / Royal Victoria Hospital, 687 Pine Avenue West, Montreal, QC, H3A 1A1, Canada

    Jacques Genest

Authors
  1. Iulia Iatan
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  2. Aurélien Palmyre
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  3. Sarah Alrasheed
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  4. Isabelle Ruel
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  5. Jacques Genest
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Corresponding author

Correspondence to Jacques Genest.

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Iatan, I., Palmyre, A., Alrasheed, S. et al. Genetics of Cholesterol Efflux. Curr Atheroscler Rep 14, 235–246 (2012). https://doi.org/10.1007/s11883-012-0247-y

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  • DOI: https://doi.org/10.1007/s11883-012-0247-y

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