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https://hdl.handle.net/20.500.14279/3677
Τίτλος: | Secretory phospholipase A2-IIA and cardiovascular disease: a mendelian randomization study | Συγγραφείς: | Holmes, Michael Vaclav Simon, Tabassome Exeter, Holly J. Folkersen, Lasse Asselbergs, Folkert W. Guardiola, Montse Cooper, Jackie A. Palmen, Jutta A. Hubacek, Jaroslav Alois Carruthers, Kathryn F. Horne, Benjamin D. Adamkova, Vera Baldassarre, Damiano Veglia, Fabrizio Holdt, Lesca Miriam Beutner, Frank Spiering, Wilko Gansevoort, Ron T. Navis, Gerjan J. Breitling, Lutz Philipp H Brenner, Hermann Hermann Olsson, Anders G. Thiery, Joachim J. Dallmeier, Dhayana Boer, Jolanda Ma A Stephens, Jeffrey W. Hofker, Marten Tedgui, Alain S. Watkins, Hugh C. Hofman, Albert Uitterlinden, Andre Gerardus Piťha, Jan Onland-Moret, N. Charlotte Ford, Ian Cramer, Maarten Jan M Nathoe, H. Klungel, Olaf H H Kumari, Meena Whincup, Peter H. Morrow, David A. Morris, Richard W. Braund, Peter S. Hall, Alistair S. Doevendans, Pieter A F M Trip, Mieke D. Price, Jackie F. Tobin, Martin D. Hamsten, Anders Koenig, Wolfgang Nicolaides, Andrew N. Teupser, Daniel Day, Ian N.M. Jukema, Johan Wouter Outer Carlquist, John F. Gaunt, Tom R. Sattar, Naveed A. Tsimikas, Sotirios Fox, Keith A.A. Schwartz, Gregory G. Lawlor, Debbie A. Sandhu, Manjinder S. Poledne, Rudolf Maitland-van Der Zee, Anke Hilse Khaw, Kay Tee T Eriksson, Per Olof Keating, Brendan J. Van Der Harst, Pim Mehta, Shamir R. Yusuf, Salim M. Brunisholz, Kimberly D. Witteman, Jacqueline C M Franco, Oscar H. De Knijff, Peter Tybjærg-Hansen, Anne Rader, Daniel J. Farrall, Martin J. Verschuren, Jeffrey J W Samani, Nilesh Kivimaki, Mika Humphries, Steve Eric Anderson, Jeffrey L. Danchin, N. Boekholdt, S. Matthijs Palmer, Tom M. Pare, Guillaume J. Hingorani, Aroon D. Sabatine, Marc S. Mallat, Ziad Goel, Anuj K. Casas, Juan Pablo Talmud, Philippa J. Mega, Jessica Van Iperen, Erik P A Tremoli, Elena Leusink, Maarten Trompet, Stella Hovingh, Gerald Kees Dehghan, Abbas Jan Nelson, Christopher P. Kotti, Salma Mateo Leach, Irene Scholz, Markus R. Haase, Christiane L. Rothenbacher, Dietrich Swerdlow, Daniel I. Franco-Cereceda, Anders Kuchenbaecker, Karoline B. Staines-Urias, Eleonora Van 'T Hooft, Ferdinand M. Gertow, Karl De Faire, Ulf H. Panayiotou, Andrie G. |
Major Field of Science: | Medical and Health Sciences | Field Category: | Clinical Medicine | Λέξεις-κλειδιά: | Cardiovascular diseases;Drug development;Epidemiology;Genetics;Mendelian randomization | Ημερομηνία Έκδοσης: | 19-Νοε-2013 | Πηγή: | Journal of the American College of Cardiology, 2013, vol. 62, no. 21, pp. 1966-1976 | Volume: | 62 | Issue: | 21 | Start page: | 1966 | End page: | 1976 | Περιοδικό: | Journal of the American College of Cardiology | Περίληψη: | Objectives This study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease. Background Higher circulating levels of sPLA2-IIA mass or sPLA 2 enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA2 inhibitor (varespladib) was stopped prematurely for lack of efficacy. Methods We conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA2-IIA isoenzyme, as an instrumental variable. Results PLA2G2A rs11573156 C allele associated with lower circulating sPLA2-IIA mass (38% to 44%) and sPLA2 enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA2-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA 2 enzyme activity and MVE. Conclusions Reducing sPLA2-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events. | URI: | https://hdl.handle.net/20.500.14279/3677 | ISSN: | 15583597 | DOI: | 10.1016/j.jacc.2013.06.044 | Rights: | © American College of Cardiology Foundation | Type: | Article | Affiliation: | University College London Hôpital Saint-Antoine Université Pierre et Marie Curie Karolinska Institutet Karolinska University Hospital University Medical Center Utrecht Durrer Center for Cardiogenetic Research Universitat Rovira i Virgili Institute for Clinical and Experimental Medicine The University of Edinburgh Intermountain Medical Center University of Utah School of Medicine Harvard University University of Amsterdam University of Pennsylvania Utrecht University Leiden University Erasmus University Rotterdam Netherlands Consortium for Healthy Aging University of Leicester Glenfield Hospital Hôpital Européen Georges Pompidou Universite Paris University of Leipzig Copenhagen University Hospital Ulm University German Cancer Research Center University of Cambridge London School of Hygiene and Tropical Medicine University of Oxford Cyprus University of Technology Universitá di Milano Centro Cardiologico Monzino University Hospital Leipzig University of Leipzig University Medical Center Groningen University of Ulm Medical Center Swansea University University of Groningen Inserm Research Unit St George's University of London University of Leeds Linköping University Imperial College London Ludwig Maximilians University University of Bristol University of Glasgow University of California University of Colorado Childrens Hospital of Philadelphia McMaster University Interuniversity Cardiology Institute of the Netherlands Leiden University Penn Heart and Vascular Center University of Warwick |
Publication Type: | Peer Reviewed |
Εμφανίζεται στις συλλογές: | Άρθρα/Articles |
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