title: Genetics of cholesterol efflux.
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.
authors.affiliation: Cardiovascular Research Laboratories, Division of Cardiology, Department of Biochemistry, Faculty of Medicine, McGill University, Montreal, QC, Canada.
authors.forename: Iulia
authors.initials: I
authors.lastname: Iatan
authors.forename: Aurélien
authors.initials: A
authors.lastname: Palmyre
authors.forename: Sarah
authors.initials: S
authors.lastname: Alrasheed
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ruel
authors.forename: Jacques
authors.initials: J
authors.lastname: Genest
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000235:genetics; D002784:Cholesterol / Q000235:genetics* / Q000378:metabolism; D003327:Coronary Disease / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D009154:Mutation; D010641:Phenotype
chemical_list: D004247:DNA; D002784:Cholesterol