Genetics of cholesterol efflux

Curr Atheroscler Rep. 2012 Jun;14(3):235-46. doi: 10.1007/s11883-012-0247-y.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Biological Transport / genetics
  • Cholesterol / genetics*
  • Cholesterol / metabolism
  • Coronary Disease / genetics*
  • Coronary Disease / metabolism
  • DNA / genetics*
  • Genome-Wide Association Study
  • Humans
  • Lipid Metabolism / genetics*
  • Mutation*
  • Phenotype


  • DNA
  • Cholesterol