Lack of Association Between the Trp719Arg Polymorphism in Kinesin-Like Protein-6 and Coronary Artery Disease in 19 Case-Control Studies

Themistocles L. Assimes; Hilma Hólm; Sekar Kathiresan; Muredach P. Reilly; Gudmar Thorleifsson; Benjamin F. Voight; Jeanette Erdmann; Christina Willenborg; Dhananjay Vaidya; Changchun Xie; Chris C. Patterson; Thomas M. Morgan; Mary Susan Burnett; Mingyao Li; Mark A. Hlatky; Joshua W. Knowles; John R. Thompson; Devin Absher; Carlos Iribarren; Alan Go; Stephen P. Fortmann; Stephen Sidney; Neil Risch; Hua Tang; Richard M. Myers; Klaus Berger; Monika Stoll; Svati H. Shah; Gudmundur Thorgeirsson; Karl Andersen; Aki S. Havulinna; J. Enrique Herrera; Nauder Faraday; Yoonhee Kim; Brian G. Kral; Rasika A. Mathias; Ingo Ruczinski; Bhoom Suktitipat; Alexander F. Wilson; Lisa R. Yanek; Lewis C. Becker; Patrick Linsel-Nitschke; Wolfgang Lieb; Inke R. König; Christian Hengstenberg; Marcus Fischer; Klaus Stark; Wibke Reinhard; Janina Winogradow; Martina Grassl; Anika Grosshennig; Michael Preuss; Stefan Schreiber; H.-Erich Wichmann; Christa Meisinger; Jean Yee; Yechiel Friedlander; Ron Do; James B. Meigs; Gordon Williams; David M. Nathan; Calum A. MacRae; Liming Qu; Robert L. Wilensky; William H. Matthai; Atif N. Qasim; Hakon Hakonarson; Augusto D. Pichard; Kenneth M. Kent; Lowell Satler; Joseph M. Lindsay; Ron Waksman; Christopher W. Knouff; Dawn M. Waterworth; Max C. Walker; Vincent E. Mooser; Jaume Marrugat; Gavin Lucas; Isaac Subirana; Joan Sala; Rafael Ramos; Nicola Martinelli; Oliviero Olivieri; Elisabetta Trabetti; Giovanni Malerba; Pier Franco Pignatti; Candace Guiducci; Daniel Mirel; Melissa Parkin; Joel N. Hirschhorn; Rosanna Asselta; Stefano Duga; Kiran Musunuru; Mark J. Daly; Shaun Purcell; Sandra Eifert; Peter S. Braund; Benjamin J. Wright; Anthony J. Balmforth; Stephen G. Ball; Willem H. Ouwehand; Panos Deloukas; Michael Scholz; Francois Cambien; Andreas Huge; Thomas Scheffold; Veikko Salomaa; Domenico Girelli; Christopher B. Granger; Leena Peltonen; Pascal P. McKeown; David Altshuler; Olle Melander; Joseph M. Devaney; Stephen E. Epstein; Daniel J. Rader; Roberto Elosua; James C. Engert; Sonia S. Anand; Alistair S. Hall; Andreas Ziegler; Christopher J. O'Donnell; John A. Spertus; David Siscovick; Stephen M. Schwartz; Diane Becker; Unnur Thorsteinsdottir; Kari Stefansson; Heribert Schunkert; Nilesh J. Samani; Thomas Quertermous; Wellcome Trust Case Control Consortium, Cardiogenics

doi:10.1016/j.jacc.2010.06.022

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Lack of Association Between the Trp719Arg Polymorphism in Kinesin-Like Protein-6 and Coronary Artery Disease in 19 Case-Control Studies

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Lack of Association Between the Trp719Arg Polymorphism in Kinesin-Like Protein-6 and Coronary Artery Disease in 19 Case-Control Studies

Themistocles L. Assimes, Hilma Hólm, Sekar Kathiresan, Muredach P. Reilly, Gudmar Thorleifsson, Benjamin F. Voight, Jeanette Erdmann, Christina Willenborg, Dhananjay Vaidya, Changchun Xie, …

Journal of the American College of Cardiology, Vol.56(19), pp.1552-1563

02/11/2010

DOI: https://doi.org/10.1016/j.jacc.2010.06.022

PMCID: PMC3084526

PMID: 20933357

Abstract

coronary artery disease

KIF6

kinesin-like protein 6

myocardial infarction

polymorphism

We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455), and clinical coronary artery disease (CAD). Recent prospective studies suggest that carriers of the 719Arg allele in KIF6are at increased risk of clinical CAD compared with noncarriers. The KIF6Trp719Arg polymorphism (rs20455) was genotyped in 19 case-control studies of nonfatal CAD either as part of a genome-wide association study or in a formal attempt to replicate the initial positive reports. A total of 17,000 cases and 39,369 controls of European descent as well as a modest number of South Asians, African Americans, Hispanics, East Asians, and admixed cases and controls were successfully genotyped. None of the 19 studies demonstrated an increased risk of CAD in carriers of the 719Arg allele compared with noncarriers. Regression analyses and fixed-effects meta-analyses ruled out with high degree of confidence an increase of ≥2% in the risk of CAD among European 719Arg carriers. We also observed no increase in the risk of CAD among 719Arg carriers in the subset of Europeans with early-onset disease (younger than 50 years of age for men and younger than 60 years of age for women) compared with similarly aged controls as well as all non-European subgroups. The KIF6Trp719Arg polymorphism was not associated with the risk of clinical CAD in this large replication study.

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Title: Lack of Association Between the Trp719Arg Polymorphism in Kinesin-Like Protein-6 and Coronary Artery Disease in 19 Case-Control Studies
Creators - without role: Themistocles L. Assimes - Stanford University
Hilma Hólm - deCODE Genetics
Sekar Kathiresan - Massachusetts General Hospital
Muredach P. Reilly - University of Pennsylvania
Gudmar Thorleifsson - deCODE Genetics
Benjamin F. Voight - Broad Institute
Jeanette Erdmann - University of Lübeck
Christina Willenborg - University of Lübeck
Dhananjay Vaidya - Johns Hopkins University
Changchun Xie - Population Health Research Institute
Chris C. Patterson - Queen's University Belfast
Thomas M. Morgan - Vanderbilt University
Mary Susan Burnett - MedStar Washington Hospital Center
Mingyao Li - University of Pennsylvania
Mark A. Hlatky - Stanford University
Joshua W. Knowles - Stanford University
John R. Thompson - University of Leicester
Devin Absher - HudsonAlpha Institute for Biotechnology
Carlos Iribarren - Kaiser Permanente
Alan Go - Kaiser Permanente
Stephen P. Fortmann - Stanford University
Stephen Sidney - Kaiser Permanente
Neil Risch - University of California, San Francisco
Hua Tang - Stanford University
Richard M. Myers - HudsonAlpha Institute for Biotechnology
Klaus Berger - University of Münster
Monika Stoll - Leibniz Association
Svati H. Shah - Duke University
Gudmundur Thorgeirsson - University of Iceland
Karl Andersen - University of Iceland
Aki S. Havulinna - National Institutes of Health
J. Enrique Herrera - Department of Medicine, The Johns Hopkins School of Medicine, Baltimore, Maryland
Nauder Faraday - Johns Hopkins Medicine
Yoonhee Kim - National Institutes of Health
Brian G. Kral - Johns Hopkins University
Rasika A. Mathias - Johns Hopkins University
Ingo Ruczinski - Johns Hopkins University
Bhoom Suktitipat - Johns Hopkins University
Alexander F. Wilson - National Institutes of Health
Lisa R. Yanek - Johns Hopkins University
Lewis C. Becker - Johns Hopkins University
Patrick Linsel-Nitschke - University of Lübeck
Wolfgang Lieb - University of Lübeck
Inke R. König - University of Lübeck
Christian Hengstenberg - University of Regensburg
Marcus Fischer - University of Regensburg
Klaus Stark - University of Regensburg
Wibke Reinhard - University of Regensburg
Janina Winogradow - University of Regensburg
Martina Grassl - University of Regensburg
Anika Grosshennig - Medizinische Klinik II, Universität zu Lübeck, Lübeck, Germany
Michael Preuss - University of Lübeck
Stefan Schreiber - Kiel University
H.-Erich Wichmann - Ludwig-Maximilians-Universität München
Christa Meisinger - Augsburg University
Jean Yee - University of Washington
Yechiel Friedlander - Hebrew University of Jerusalem
Ron Do - McGill University
James B. Meigs - Harvard University
Gordon Williams - Harvard University
David M. Nathan - Harvard University
Calum A. MacRae - Harvard University
Liming Qu - University of Pennsylvania
Robert L. Wilensky - University of Pennsylvania
William H. Matthai - University of Pennsylvania
Atif N. Qasim - University of Pennsylvania
Hakon Hakonarson - Children's Hospital of Philadelphia
Augusto D. Pichard - MedStar Washington Hospital Center
Kenneth M. Kent - MedStar Washington Hospital Center
Lowell Satler - MedStar Washington Hospital Center
Joseph M. Lindsay - MedStar Washington Hospital Center
Ron Waksman - Stanford University
Christopher W. Knouff - GlaxoSmithKline
Dawn M. Waterworth - GlaxoSmithKline
Max C. Walker - GlaxoSmithKline
Vincent E. Mooser - GlaxoSmithKline
Jaume Marrugat - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública
Gavin Lucas - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública
Isaac Subirana - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública
Joan Sala - Biomedica
Rafael Ramos - University of Girona
Nicola Martinelli - University of Verona
Oliviero Olivieri - University of Verona
Elisabetta Trabetti - University of Verona
Giovanni Malerba - University of Verona
Pier Franco Pignatti - University of Verona
Candace Guiducci - Broad Institute
Daniel Mirel - Broad Institute
Melissa Parkin - Broad Institute
Joel N. Hirschhorn - Broad Institute
Rosanna Asselta - University of Milan
Stefano Duga - University of Milan
Kiran Musunuru - Massachusetts General Hospital
Mark J. Daly - Broad Institute
Shaun Purcell - Broad Institute
Sandra Eifert - Ludwig-Maximilians-Universität München
Peter S. Braund - University of Leicester
Benjamin J. Wright - University of Leicester
Anthony J. Balmforth - University of Leeds
Stephen G. Ball - University of Leeds
Willem H. Ouwehand - University of Cambridge
Panos Deloukas - Wellcome Sanger Institute
Michael Scholz - Trium Analysis Online GmbH, Munich, Germany
Francois Cambien - Marie Curie
Andreas Huge - University of Münster
Thomas Scheffold - Institute for Heart and Circulation Research of the University of Witten/Herdecke, Dortmund, Germany
Veikko Salomaa - Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
Domenico Girelli - University of Verona
Christopher B. Granger - Duke Medical Center
Leena Peltonen - Broad Institute
Pascal P. McKeown - Queen's University Belfast
David Altshuler - Massachusetts General Hospital
Olle Melander - Lund University
Joseph M. Devaney - MedStar Health
Stephen E. Epstein - MedStar Health
Daniel J. Rader - University of Pennsylvania
Roberto Elosua - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública
James C. Engert - McGill University
Sonia S. Anand - McMaster University
Alistair S. Hall - University of Leeds
Andreas Ziegler - Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Lübeck, Germany
Christopher J. O'Donnell - Massachusetts General Hospital
John A. Spertus - University of Missouri–Kansas City
David Siscovick - University of Washington
Stephen M. Schwartz - University of Washington
Diane Becker - Department of Medicine, The Johns Hopkins School of Medicine, Baltimore, Maryland
Unnur Thorsteinsdottir - deCODE Genetics
Kari Stefansson - deCODE Genetics
Heribert Schunkert - Medizinische Klinik II, Universität zu Lübeck, Lübeck, Germany
Nilesh J. Samani - University of Leicester
Thomas Quertermous - Stanford University School of Medicine
Wellcome Trust Case Control Consortium, Cardiogenics
Publication Details: Journal of the American College of Cardiology, Vol.56(19), pp.1552-1563
Publisher: Elsevier Inc
Grant note: AstraZeneca German Migraine & Headache Society (DMKG) McNeil Pharma Medtronic GlaxoSmithKline Berlin Chemie Boots Healthcare Merck MSD Sharp & Dohme and Pfizer
Identifiers: 9938605508331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article