title: Genetics for the Identification of Lipid Targets Beyond PCSK9.
abstract: From studies of rare families to genome-wide associations in populations, understanding of human genetics has accelerated the search for new drug targets for the prevention of atherosclerotic cardiovascular disease. DNA sequencing and genome-wide analyses of DNA markers have illuminated rare as well as common variants in genes that regulate lipids and ultimately atherosclerosis risk. A recent innovative approach called Mendelian randomization can endorse specific genes and variants as causative not just for lipid disturbances, but also for clinical cardiovascular end points. This knowledge helps prioritize the candidate genes and proteins in the drug development pipeline. In this review, we focus on dyslipidemia drug targets traceable to human genetic studies, including statins and ezetimibe, as well as promising new classes such as inhibitors of proprotein convertase subtilisin kexin 9, apolipoprotein B, microsomal triglyceride transfer protein, cholesteryl ester transfer protein, angiopoietin-like proteins types 3 and 4 and apolipoprotein C-III. Several of these new agents have attained or are closing in on "prime-time readiness" for clinical use in specific situations.
authors.affiliation: Department of Medicine and Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors.forename: Linda R
authors.initials: LR
authors.lastname: Wang
authors.affiliation: Department of Medicine and Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada. Electronic address: hegele@robarts.ca.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hegele
mesh_terms: D050197:Atherosclerosis / Q000097:blood / Q000235:genetics / Q000517:prevention & control; D004247:DNA / Q000235:genetics*; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods*; D055106:Genome-Wide Association Study; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D000071449:Proprotein Convertase 9 / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D000960:Hypolipidemic Agents; D004247:DNA; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9