Please use this identifier to cite or link to this item: https://ktisis.cut.ac.cy/handle/10488/10079
Title: PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study
Authors: Schmidt, Amand F. 
Swerdlow, Daniel I. 
Holmes, Michael Vaclav 
Patel, Riyaz Suleman 
Fairhurst-Hunter, Zammy 
Lyall, Donald M. 
Hartwig, Fernando Pires 
Horta, Bernardo Lessa 
Hyppönen, Elina 
Power, Chris 
Moldovan, Max V. 
Lind, Lars 
Ingelsson, Erik 
Pazoki, Raha 
Franco, Oscar H. 
Hofman, Albert 
Uitterlinden, André G. 
Dehghan, Abbas 
Teumer, Alexander 
Baumeister, Sebastian Edgar 
Pell, Jill P. 
Mahajan, Anubha 
Dörr, Marcus 
Lerch, Markus M. 
Völker, Uwe U. 
Smith, Daniel J. 
Meade, Tom W. 
Maitland-van Der Zee, Anke Hilse 
Baranova, Ekaterina V. 
Young, Robin 
Ford, Ian 
Campbell, Archie 
Ridker, Paul M. 
Van Iperen, Erik P.A 
Padmanabhan, Sandosh 
Bots, Michiel L. 
Grobbee, Diederick E. 
Froguel, Philippe H. 
Thuillier, Dorothée 
Balkau, Beverley J. 
Bonnefond, Amélie 
Cariou, Bertrand 
Smart, Melissa C. 
Chasman, Daniel I. 
Bao, Yanchun 
Hovingh, Gerald Kees 
Kumari, Meena 
Reiner, Alexander Paul 
Lange, Leslie A. 
Ritchie, Marylyn D. 
Asselbergs, Folkert W. 
Casas, Juan Pablo 
Keating, Brendan J. 
Demuth, Ilja 
Marques-Vidal, Pedro 
Preiss, David J. 
Hingorani, Aroon D. 
Sattar, Naveed A. 
Norman, Kristina 
Steinhagen-Thiessen, Elisabeth 
Demuth, Juri 
Bertram, Lars 
Liu, Tian 
Coassin, Stefan 
Willeit, Johann 
Nicolaides, Andrew N. 
Kiechl, Stefan 
Willeit, Karin 
Mason, Dan 
Wright, John P. 
Morris, Richard W. 
Wanamethee, Goya 
Whincup, Peter Hynes 
Ben-Shlomo, Yoav 
McLachlan, Stela 
Price, Jackie F. 
Panayiotou, Andrie G. 
Kivimaki, Mika 
Welch, Catherine A. 
Sanchez-Galvez, Adelaida 
Onland-Moret, N. Charlotte 
Van der Schouw, Y. T. 
Matullo, Giuseppe 
Fiorito, Giovanni 
Guarrera, Simonetta 
Sacerdote, Carlotta 
Wareham, Nicholas J.J. 
Larson, Eric B. 
Langenberg, Claudia 
Scott, Robert A. 
Luan, Jian'an 
Bobak, Martin 
Malyutina, Sofia 
Pająk, Andrzej 
Kubinova, Růžena 
Tamosiunas, Abdonas 
Pikhart, Hynek 
Husemoen, Lise Lotte Nystrup 
Crosslin, David R. 
Grarup, Niels 
Pedersen, Oluf Borbye Orbye 
Hansen, Torben Froestrup 
Linneberg, Allan 
Simonsen, Kenneth Starup 
Cooper, Jackie A. 
Humphries, Steve Eric 
Brilliant, Murray H. 
Kitchner, Terrie E. 
Hakonarson, Håkon H. 
De Andrade, Mariza De 
Carrell, David S. 
McCarty, Catherine A. 
Kirchner, H. Lester 
Roden, Dan M. 
Denny, Joshua C. 
Carty, Cara L. 
Hancock, Stephen John 
Attia, John 
Holliday, Elizabeth G. 
O'Donnell, Martin 
Völzke, Henry 
Yusuf, Salim 
Chong, Michael 
Pare, Guillaume 
Van Der Harst, Pim 
Said, Michael Abdullah 
Eppinga, Ruben N. 
Verweij, Niek 
Snieder, Harold 
Christen, Tim 
Mook-Kanamori, Dennis Owen 
Ward, Joey 
Gustafsson, Stefan 
Major Field of Science: Medical and Health Sciences
Field Category: Health Sciences
Keywords: Heart disease;LDL cholesterol;Diabetes
Issue Date: 1-Feb-2017
Source: The Lancet Diabetes and Endocrinology, 2017, vol. 5, no. 2, pp. 97-105
Volume: 5
Issue: 2
Start page: 97
End page: 105
Journal: The Lancet Diabetes and Endocrinology 
Abstract: Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk. Methods In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores. Findings Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0·09 mmol/L, 95% CI 0·02 to 0·15), bodyweight (1·03 kg, 0·24 to 1·82), waist-to-hip ratio (0·006, 0·003 to 0·010), and an odds ratio for type diabetes of 1·29 (1·11 to 1·50). Based on the collected data, we did not identify associations with HbA1c (0·03%, −0·01 to 0·08), fasting insulin (0·00%, −0·06 to 0·07), and BMI (0·11 kg/m2, −0·09 to 0·30). Interpretation PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefits of PCSK9 inhibitor treatment, as was previously done for statins. Funding British Heart Foundation, and University College London Hospitals NHS Foundation Trust (UCLH) National Institute for Health Research (NIHR) Biomedical Research Centre.
ISSN: 2213-8595
DOI: 10.1016/S2213-8587(16)30396-5
Rights: © The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license.
Type: Article
Affiliation : University College London 
University of Oxford 
Emory Clinic 
Wellcome Trust Centre for Human Genetics 
University of Glasgow 
Universidade Federal de Pelotas 
University of South Australia 
UCL Institute of Child Health 
ICIN-Netherlands Heart Institute 
University of Amsterdam 
Research Group On Geriatrics 
Charité-Universitätsmedizin Berlin 
Universitat zu Lubeck 
Max Planck Institute 
Medizinische Universitat Innsbruck 
Bradford Royal Infirmary 
University of Bristol 
St George's University of London 
University of Edinburgh 
Tyoterveyslaitos 
Centre Hospitalier Universitaire Vaudois 
Vascular Screening and Diagnostic Centre 
Cyprus University of Technology 
University Medical Center Utrecht 
Universita degli Studi di Torino 
Human Genetics Foundation 
University of Cambridge 
Institute of Internal and Preventive Medicine 
Collegium Medicum Uniwersytet Jagiellonskiego 
National Institute of Public Health Prague 
Lithuanian University of Health Sciences 
Research Centre for Prevention and Health 
Kobenhavns Universitet 
Marshfield Clinic Research Institute 
Childrens Hospital of Philadelphia 
Group Health Cooperative 
Essentia Institute of Rural Health 
Geisinger Medical Center 
Washington University 
Mayo Clinic 
Division of Clinical Pharmacology 
Vanderbilt University 
Fred Hutchinson Cancer Research Center 
Newcastle University 
Hunter Medical Research Institute 
Population Health Research Institute 
McMaster University 
University of Groningen 
Leiden University Medical Center 
Uppsala Universitet 
Erasmus University Medical Center 
University Medicine Greifswald 
Universitat Regensburg 
Deutsches Zentrum fur Herz-Kreislauf-Forschung e. V. 
London School of Hygiene and Tropical Medicine 
Universite Lille 2 Droit et Sante 
Genomique Integrative et Modelisation des Maladies Metaboliques 
Centre for Epidemiology and Population Health (CESP) 
Centre Hospitalier Universitaire de Nantes 
University of Essex 
Nuffield Department of Clinical Medicine 
Brigham and Women's Hospital 
University of North Carolina at Chapel Hill School of Medicine 
Geisinger Health System 
Appears in Collections:Άρθρα/Articles

Files in This Item:
File Description SizeFormat
Panayiotou.pdf590.08 kBAdobe PDFView/Open
CORE Recommender
Show full item record

SCOPUSTM   
Citations

236
checked on Dec 3, 2022

WEB OF SCIENCETM
Citations 50

229
Last Week
0
Last month
3
checked on Dec 4, 2022

Page view(s)

329
Last Week
2
Last month
6
checked on Dec 6, 2022

Download(s)

76
checked on Dec 6, 2022

Google ScholarTM

Check

Altmetric


Items in KTISIS are protected by copyright, with all rights reserved, unless otherwise indicated.