Journal Article

Coding Variation in ANGPTL4, LPL, and SVEP1 and the Risk of Coronary Disease

Jackson, Rebecca D, Varga, Tibor V, Morris, Andrew D, Schick, Ursula M, Howson, Joanna M M, Mihailov, Evelin, Weeke, Peter E, McCarthy, Mark I, Van Zuydam, Natalie R, Erdmann, Jeanette, Farrall, Martin, Hveem, Kristian, Ferrario, Marco, Merlini, Piera A, Hengstenberg, Christian, Kriebel, Jennifer, Akinsanya, Karen O, Martinelli, Nicola, Tregouet, David, Waldenberger, Melanie, Franke, Andre, Asselta, Rosanna, Denny, Josh C, Kraja, Aldi T, Peloso, Gina M, El-Mokhtari, Nour Eddine, Esko, Tõnu, Alver, Maris, Webb, Thomas R, König, Inke R, Kuulasmaa, Kari, Ferrario, Paola G, Robertson, Neil R, Masca, Nicholas G D, Dube, Marie-Pierre, Scott, Robert A, Nikpay, Majid, Jukema, J Wouter, Willenberg, Christina, Shaffer, Christian M, Moebus, Susanne, Kruppa, Jochen, Danesh, John, Newton-Cheh, Christopher, Perola, Markus, Vogt, Thomas F, Jansson, Jan-Håkan, Marziliano, Nicola, Kee, Frank, Zhang, He, Sattar, Naveed, Müller-Nurasyid, Martina, Olivieri, Oliviero, Kooperberg, Charles, Liu, Chunyu, Escher, Stefan A, Meisinger, Christa, Heilmann, Stefanie, Nordestgaard, Børge G, Stahl, Eli, Goel, Anuj, Zeng, Lingyao, van Cape

2016

Overview

Searching for genes in which loss-of-function mutations confer protection against disease is a strategy to identity drug targets. This study reports an association between loss-of-function mutations in ANGPTL4 and protection against coronary artery disease. Although genomewide association studies have identified more than 56 loci associated with the risk of coronary artery disease, 1 – 3 the disease-associated variants are typically common (minor-allele frequency >5%) and located in noncoding sequences; this has made it difficult to pinpoint causal genes and affected pathways. This lack of a causal mechanism has in part hindered the immediate translation of the findings of genomewide association studies into new therapeutic targets. However, the discovery of rare or low-frequency coding-sequence variants that affect the risk of coronary artery disease has facilitated advances in the prevention and treatment of disease. The most recent example . . .

• Publisher: Massachusetts Medical Society
• Subject: Aged / Alleles / Angiopoietin / Angiopoietin-Like Protein 4 / Angiopoietins - genetics / Basic Medicine / Cardiovascular disease / Cell Adhesion Molecules - genetics / Cholesterol / Coronary artery / Coronary Artery Disease - genetics / Coronary vessels / DNA sequencing / Female / Gene frequency / Genes / Genotyping / Genotyping Techniques / Heart diseases / Humans / Lipase / Lipoprotein lipase / Lipoprotein Lipase - antagonists & inhibitors / Lipoprotein Lipase - genetics / Lipoprotein Lipase - metabolism / Male / Medical and Health Sciences / Medical Genetics and Genomics (including Gene Therapy) / Medicin och hälsovetenskap / Medicinsk genetik och genomik (Här ingår: Genterapi) / Medicinska och farmaceutiska grundvetenskaper / Middle Aged / Mutation / Mutation, Missense / Myocardial infarction / Nucleotide sequence / Risk Factors / Sequence Analysis, DNA / Therapeutic applications / Triglycerides / Triglycerides - blood / Triglycerides - genetics