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Genetics of HDL-C: A Causal Link to Atherosclerosis?

  • Genetics (AJ Marian, Section Editor)
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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.

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Conflict of Interest

Julian C. van Capelleveen declares no conflict of interest.

Andrea E. Bochem declares no conflict of interest.

Mahdi M. Motazacker declares no conflict of interest.

G. Kees Hovingh received payment for development of educational presentations from Pfizer and Genzyme.

John J. P. Kastelein is a consultant to AstraZeneca, Aegerion, Genzyme, Isis Pharmaceuticals, Boehringer-Ingelheim, Roche, Pfizer, Eli Lilly, Sanofi, MSD, Cerenis, Regeneron, and Novartis and has received payment for development of educational presentations from AstraZeneca, Aegerion, Genzyme, Isis Pharmaceuticals, Roche, Pfizer, Eli Lilly, MSD, and Cerenis.

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  1. Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    Julian C. van Capelleveen, Andrea E. Bochem, G. Kees Hovingh & John J. P. Kastelein

  2. Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands

    M. Mahdi Motazacker

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  1. Julian C. van Capelleveen
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van Capelleveen, J.C., Bochem, A.E., Motazacker, M.M. et al. Genetics of HDL-C: A Causal Link to Atherosclerosis?. Curr Atheroscler Rep 15, 326 (2013). https://doi.org/10.1007/s11883-013-0326-8

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