title: Genetics of HDL-C: a causal link to atherosclerosis?
abstract: Prospective epidemiological studies have consistently reported an inverse association between HDL cholesterol (HDL-C) levels and the risk of cardiovascular disease (CVD). However, large intervention trials on HDL-C-increasing drugs and recent Mendelian randomization studies have questioned a causal relationship between HDL-C and atherosclerosis. HDL-C levels have been shown to be highly heritable, and the combination of HDL-C-associated SNPs in recent large-scale genome-wide association studies (GWAS) only explains a small proportion of this heritability. As a large part of our current understanding of HDL metabolism comes from genetic studies, further insights in this research field may aid us in elucidating HDL functionality in relation to CVD risk. In this review we focus on the question of whether genetically defined HDL-C levels are associated with risk of atherosclerosis. We also discuss the latest insights for HDL-C-associated genes and recent GWAS data.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Julian C
authors.initials: JC
authors.lastname: van Capelleveen
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Bochem
authors.forename: M Mahdi
authors.initials: MM
authors.lastname: Motazacker
authors.forename: G Kees
authors.initials: GK
authors.lastname: Hovingh
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
mesh_terms: D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism; D008076:Cholesterol, HDL / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D008076:Cholesterol, HDL