Current Atherosclerosis Reports

, Volume 14, Issue 3, pp 235–246

Genetics of Cholesterol Efflux

  • Iulia Iatan
  • Aurélien Palmyre
  • Sarah Alrasheed
  • Isabelle Ruel
  • Jacques Genest
Genetics (AJ Marian, Section Editor)

DOI: 10.1007/s11883-012-0247-y

Cite this article as:
Iatan, I., Palmyre, A., Alrasheed, S. et al. Curr Atheroscler Rep (2012) 14: 235. doi:10.1007/s11883-012-0247-y

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.

Keywords

HDL Coronary artery disease Genetics Cholesterol efflux ABCA1 Apo AI ABCG1 SR-BI Cholesteryl ester hydrolases NPC1 NPC2 LIPA SMPD1 StAR D3 miRNA Genome wide association studies 

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Iulia Iatan
    • 1
  • Aurélien Palmyre
    • 2
  • Sarah Alrasheed
    • 3
  • Isabelle Ruel
    • 4
  • Jacques Genest
    • 5
  1. 1.Cardiovascular Research Laboratories, Division of Cardiology, Department of Biochemistry, Faculty of MedicineMcGill University and McGill University Health Center / Royal Victoria HospitalMontrealCanada
  2. 2.Magistère Européen de GénétiqueUniversité Paris Diderot - Paris 7ParisFrance
  3. 3.Cardiovascular Research Laboratories, Division of Cardiology, Department of Human Genetics, Faculty of MedicineMcGill University and McGill University Health Center / Royal Victoria HospitalMontrealCanada
  4. 4.Cardiovascular Research Laboratories, Division of CardiologyMcGill University Health Centre / Royal Victoria HospitalMontrealCanada
  5. 5.Faculty of Medicine, Novartis Chair in Medicine, Cardiovascular Research Laboratories, Division of CardiologyMcGill University and McGill University Health Center / Royal Victoria HospitalMontrealCanada

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