Polygenic Risk for Hypertriglyceridemia Can Mimic a Major Monogenic Mutation
Authors: Priska Stahel, Changting Xiao, Robert A. Hegele, Gary F. Lewis
Journal: Annals of Internal Medicine (2017)

Letters5 September 2017Polygenic Risk for Hypertriglyceridemia Can Mimic a Major Monogenic MutationPriska Stahel, PhD, Changting Xiao, PhD, Robert A. Hegele, MD, and Gary F. Lewis, MDPriska Stahel, PhDFrom Banting & Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada; Robarts Research Institute, London, Ontario, Canada; Banting & Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada., Changting Xiao, PhDFrom Banting & Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada; Robarts Research Institute, London, Ontario, Canada; Banting & Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada., Robert A. Hegele, MDFrom Banting & Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada; Robarts Research Institute, London, Ontario, Canada; Banting & Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada., and Gary F. Lewis, MDFrom Banting & Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada; Robarts Research Institute, London, Ontario, Canada; Banting & Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/L17-0182 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Background: One in 1 million persons has monogenic, familial chylomicronemia that leads to marked hypertriglyceridemia (fasting plasma triglyceride levels >10 mmol/L [>885 mg/dL]), a defect associated with an increased risk for acute pancreatitis. Several genes, including LPL, APOC2, APOA5, LMF1, and GPIHBP1, can have large-effect mutations that are sufficient to cause the phenotype of hypertriglyceridemia when they are in a simple homozygous or compound heterozygous state (1). In contrast, more than 150 common-variant loci contribute modestly to perturbed lipid levels (2). To measure the joint effects of these loci on triglyceride levels, investigators developed the triglyceride polygenic risk score (3). This ...References1. Lewis GF, Xiao C, Hegele RA. Hypertriglyceridemia in the genomic era: a new paradigm. Endocr Rev. 2015;36:131-47. [PMID: 25554923] doi:10.1210/er.2014-1062 CrossrefMedlineGoogle Scholar2. Willer CJ, Schmidt EM, Sengupta S, Peloso GM, Gustafsson S, Kanoni S, et al; Global Lipids Genetics Consortium. Discovery and refinement of loci associated with lipid levels. Nat Genet. 2013;45:1274-83. [PMID: 24097068] doi:10.1038/ng.2797 CrossrefMedlineGoogle Scholar3. Hegele RA, Ban MR, Cao H, McIntyre AD, Robinson JF, Wang J. Targeted next-generation sequencing in monogenic dyslipidemias. Curr Opin Lipidol. 2015;26:103-13. [PMID: 25692347] doi:10.1097/MOL.0000000000000163 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Banting & Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada; Robarts Research Institute, London, Ontario, Canada; Banting & Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L17-0182.This article was published at Annals.org on 25 July 2017. 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