title: Sortilin: an unusual suspect in cholesterol metabolism: from GWAS identification to in vivo biochemical analyses, sortilin has been identified as a novel mediator of human lipoprotein metabolism.
abstract: The concentration of low-density lipoprotein (LDL) cholesterol (C) in plasma is a key determinant of cardiovascular disease risk and human genetic studies have long endeavoured to elucidate the pathways that regulate LDL metabolism. Massive genome-wide association studies (GWASs) of common genetic variation associated with LDL-C in the population have implicated SORT1 in LDL metabolism. Using experimental paradigms and standards appropriate for understanding the mechanisms by which common variants alter phenotypic expression, three recent publications have presented divergent and even contradictory findings. Interestingly, although these reports each linked SORT1 to LDL metabolism, they did not agree on a mechanism to explain the association. Here, we review recent mechanistic studies of SORT1 - the first gene identified by GWAS as a determinant of plasma LDL-C to be evaluated mechanistically.
authors.affiliation: Departments of Biochemistry and Medicine, Robarts Research Institute and Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Dubé
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Johansen
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hegele
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism*; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008077:Lipoproteins, LDL / Q000235:genetics / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D002784:Cholesterol; D008077:Lipoproteins, LDL; D000099183:Sortilin