Erin Jacob1,2, Robert A Hegele3,4,5. 1. Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street, London, ON, N6A 5B7, Canada. 2. Schulich School of Medicine and Dentistry, Robarts Research Institute, Western University, 1151 Richmond Street, London, ON, N6A 5B7, Canada. 3. Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street, London, ON, N6A 5B7, Canada. hegele@robarts.ca. 4. Schulich School of Medicine and Dentistry, Robarts Research Institute, Western University, 1151 Richmond Street, London, ON, N6A 5B7, Canada. hegele@robarts.ca. 5. Department of Medicine, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street, London, ON, N6A 5B7, Canada. hegele@robarts.ca.
Abstract
PURPOSE OF REVIEW: Common DNA variants with small effects work together to create susceptibility to polygenic hypercholesterolemia. Some clinicians wonder whether patients with polygenic hypercholesterolemia have less severe clinical features compared to patients with monogenic familial hypercholesterolemia (FH) caused by rare deleterious variants. RECENT FINDINGS: Studies performed in cohorts of patients with both monogenic and polygenic hypercholesterolemia have assessed lipid levels, non-invasive markers of atherosclerosis, and clinical end points, including major adverse cardiovascular events. The totality of data suggests a gradient across genotypes. Specifically, individuals with polygenic hypercholesterolemia have deleterious phenotypes that are intermediate in severity between those in patients with monogenic hypercholesterolemia and in control subjects. Although clinical variables in patients with polygenic hypercholesterolemia are less severe than in those with monogenic hypercholesterolemia, cardiovascular risk is still very high in these patients compared to controls. Patients with polygenic hypercholesterolemia must be treated assertively.
PURPOSE OF REVIEW: Common DNA variants with small effects work together to create susceptibility to polygenic hypercholesterolemia. Some clinicians wonder whether patients with polygenic hypercholesterolemia have less severe clinical features compared to patients with monogenic familial hypercholesterolemia (FH) caused by rare deleterious variants. RECENT FINDINGS: Studies performed in cohorts of patients with both monogenic and polygenic hypercholesterolemia have assessed lipid levels, non-invasive markers of atherosclerosis, and clinical end points, including major adverse cardiovascular events. The totality of data suggests a gradient across genotypes. Specifically, individuals with polygenic hypercholesterolemia have deleterious phenotypes that are intermediate in severity between those in patients with monogenic hypercholesterolemia and in control subjects. Although clinical variables in patients with polygenic hypercholesterolemia are less severe than in those with monogenic hypercholesterolemia, cardiovascular risk is still very high in these patients compared to controls. Patients with polygenic hypercholesterolemia must be treated assertively.
Authors: Philippa J Talmud; Sonia Shah; Ros Whittall; Marta Futema; Philip Howard; Jackie A Cooper; Seamus C Harrison; Kawah Li; Fotios Drenos; Frederik Karpe; H Andrew W Neil; Olivier S Descamps; Claudia Langenberg; Nicholas Lench; Mika Kivimaki; John Whittaker; Aroon D Hingorani; Meena Kumari; Steve E Humphries Journal: Lancet Date: 2013-02-22 Impact factor: 79.321
Authors: Tanya M Teslovich; Kiran Musunuru; Albert V Smith; Andrew C Edmondson; Ioannis M Stylianou; Masahiro Koseki; James P Pirruccello; Samuli Ripatti; Daniel I Chasman; Cristen J Willer; Christopher T Johansen; Sigrid W Fouchier; Aaron Isaacs; Gina M Peloso; Maja Barbalic; Sally L Ricketts; Joshua C Bis; Yurii S Aulchenko; Gudmar Thorleifsson; Mary F Feitosa; John Chambers; Marju Orho-Melander; Olle Melander; Toby Johnson; Xiaohui Li; Xiuqing Guo; Mingyao Li; Yoon Shin Cho; Min Jin Go; Young Jin Kim; Jong-Young Lee; Taesung Park; Kyunga Kim; Xueling Sim; Rick Twee-Hee Ong; Damien C Croteau-Chonka; Leslie A Lange; Joshua D Smith; Kijoung Song; Jing Hua Zhao; Xin Yuan; Jian'an Luan; Claudia Lamina; Andreas Ziegler; Weihua Zhang; Robert Y L Zee; Alan F Wright; Jacqueline C M Witteman; James F Wilson; Gonneke Willemsen; H-Erich Wichmann; John B Whitfield; Dawn M Waterworth; Nicholas J Wareham; Gérard Waeber; Peter Vollenweider; Benjamin F Voight; Veronique Vitart; Andre G Uitterlinden; Manuela Uda; Jaakko Tuomilehto; John R Thompson; Toshiko Tanaka; Ida Surakka; Heather M Stringham; Tim D Spector; Nicole Soranzo; Johannes H Smit; Juha Sinisalo; Kaisa Silander; Eric J G Sijbrands; Angelo Scuteri; James Scott; David Schlessinger; Serena Sanna; Veikko Salomaa; Juha Saharinen; Chiara Sabatti; Aimo Ruokonen; Igor Rudan; Lynda M Rose; Robert Roberts; Mark Rieder; Bruce M Psaty; Peter P Pramstaller; Irene Pichler; Markus Perola; Brenda W J H Penninx; Nancy L Pedersen; Cristian Pattaro; Alex N Parker; Guillaume Pare; Ben A Oostra; Christopher J O'Donnell; Markku S Nieminen; Deborah A Nickerson; Grant W Montgomery; Thomas Meitinger; Ruth McPherson; Mark I McCarthy; Wendy McArdle; David Masson; Nicholas G Martin; Fabio Marroni; Massimo Mangino; Patrik K E Magnusson; Gavin Lucas; Robert Luben; Ruth J F Loos; Marja-Liisa Lokki; Guillaume Lettre; Claudia Langenberg; Lenore J Launer; Edward G Lakatta; Reijo Laaksonen; Kirsten O Kyvik; Florian Kronenberg; Inke R König; Kay-Tee Khaw; Jaakko Kaprio; Lee M Kaplan; Asa Johansson; Marjo-Riitta Jarvelin; A Cecile J W Janssens; Erik Ingelsson; Wilmar Igl; G Kees Hovingh; Jouke-Jan Hottenga; Albert Hofman; Andrew A Hicks; Christian Hengstenberg; Iris M Heid; Caroline Hayward; Aki S Havulinna; Nicholas D Hastie; Tamara B Harris; Talin Haritunians; Alistair S Hall; Ulf Gyllensten; Candace Guiducci; Leif C Groop; Elena Gonzalez; Christian Gieger; Nelson B Freimer; Luigi Ferrucci; Jeanette Erdmann; Paul Elliott; Kenechi G Ejebe; Angela Döring; Anna F Dominiczak; Serkalem Demissie; Panagiotis Deloukas; Eco J C de Geus; Ulf de Faire; Gabriel Crawford; Francis S Collins; Yii-der I Chen; Mark J Caulfield; Harry Campbell; Noel P Burtt; Lori L Bonnycastle; Dorret I Boomsma; S Matthijs Boekholdt; Richard N Bergman; Inês Barroso; Stefania Bandinelli; Christie M Ballantyne; Themistocles L Assimes; Thomas Quertermous; David Altshuler; Mark Seielstad; Tien Y Wong; E-Shyong Tai; Alan B Feranil; Christopher W Kuzawa; Linda S Adair; Herman A Taylor; Ingrid B Borecki; Stacey B Gabriel; James G Wilson; Hilma Holm; Unnur Thorsteinsdottir; Vilmundur Gudnason; Ronald M Krauss; Karen L Mohlke; Jose M Ordovas; Patricia B Munroe; Jaspal S Kooner; Alan R Tall; Robert A Hegele; John J P Kastelein; Eric E Schadt; Jerome I Rotter; Eric Boerwinkle; David P Strachan; Vincent Mooser; Kari Stefansson; Muredach P Reilly; Nilesh J Samani; Heribert Schunkert; L Adrienne Cupples; Manjinder S Sandhu; Paul M Ridker; Daniel J Rader; Cornelia M van Duijn; Leena Peltonen; Gonçalo R Abecasis; Michael Boehnke; Sekar Kathiresan Journal: Nature Date: 2010-08-05 Impact factor: 49.962