Variant ASGR1 Associated with a Reduced Risk of Coronary Artery Disease

• Published in: The New England journal of medicine Vol. 374; no. 22; pp. 2131 - 2141
• Main Authors: Nioi, Paul, Sigurdsson, Asgeir, Thorleifsson, Gudmar, Helgason, Hannes, Agustsdottir, Arna B, Norddahl, Gudmundur L, Helgadottir, Anna, Magnusdottir, Audur, Jonasdottir, Aslaug, Gretarsdottir, Solveig, Jonsdottir, Ingileif, Steinthorsdottir, Valgerdur, Rafnar, Thorunn, Swinkels, Dorine W, Galesloot, Tessel E, Grarup, Niels, Jørgensen, Torben, Vestergaard, Henrik, Hansen, Torben, Lauritzen, Torsten, Linneberg, Allan, Friedrich, Nele, Krarup, Nikolaj T, Fenger, Mogens, Abildgaard, Ulrik, Hansen, Peter R, Galløe, Anders M, Braund, Peter S, Nelson, Christopher P, Hall, Alistair S, Williams, Michael J.A, van Rij, Andre M, Jones, Gregory T, Patel, Riyaz S, Levey, Allan I, Hayek, Salim, Shah, Svati H, Reilly, Muredach, Eyjolfsson, Gudmundur I, Sigurdardottir, Olof, Olafsson, Isleifur, Kiemeney, Lambertus A, Quyyumi, Arshed A, Rader, Daniel J, Kraus, William E, Samani, Nilesh J, Pedersen, Oluf, Thorgeirsson, Gudmundur, Masson, Gisli, Holm, Hilma, Gudbjartsson, Daniel, Sulem, Patrick, Thorsteinsdottir, Unnur, Stefansson, Kari
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 02.06.2016
• Subjects: Adult; Aged; Aged, 80 and over; Asialoglycoprotein Receptor - genetics; Base Sequence; Cardiovascular disease; Cholesterol; Cholesterol - blood; Coronary artery; Coronary Artery Disease - genetics; Coronary vessels; Female; Frameshift mutation; Gene deletion; Genetic Predisposition to Disease; Genomes; Glycoproteins; Haploinsufficiency; Heart attacks; Heart diseases; High density lipoprotein; Homeostasis; Humans; Iceland; Kaplan-Meier Estimate; Lipoproteins; Male; Middle Aged; Molecular Sequence Data; Myocardial Infarction - genetics; Nonsense mutation; Phosphatase; Population studies; Risk; Risk factors; Sequence Analysis, DNA; Serum levels; Stop codon; Triglycerides; Whites - genetics; Iceland
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa1508419

ASGR1 Variant and Coronary Risk Genetic data show that a loss-of-function variant in ASGR1 is associated with reduced levels of non-HDL cholesterol and confers protection against coronary artery disease. Epidemiologic and genetic studies have shown a causal link between levels of non–high-density lipoprotein (non-HDL) cholesterol and of low-density lipoprotein (LDL) cholesterol and the risk of coronary artery disease and myocardial infarction. 1 – 3 Non-HDL cholesterol has been shown to be a better predictor of cardiovascular risk than LDL cholesterol, since it encompasses all cholesterol-containing proatherogenic lipoproteins, including LDL cholesterol, very-low-density lipoprotein, intermediate-density lipoprotein, lipoprotein(a), and chylomicron. 4 Non-HDL cholesterol levels are calculated by subtracting HDL cholesterol levels from total cholesterol levels. Through the discovery of sequence variants that affect both cholesterol and the risk of coronary artery disease, genetic studies have . . .