Lack of association between the Trp719Arg polymorphism in kinesin-like protein-6 and coronary artery disease in 19 case-control studies.

Abstract

OBJECTIVES:

We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455), and clinical coronary artery disease (CAD).

BACKGROUND:

Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with noncarriers.

METHODS:

The KIF6 Trp719Arg 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.

RESULTS:

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.

CONCLUSIONS:

The KIF6 Trp719Arg polymorphism was not associated with the risk of clinical CAD in this large replication study.

• Authors: 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 Jr, 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, Myocardial Infarction Genetics Consortium, Wellcome Trust Case Control Consortium, Cardiogenics, 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
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 56 Issue 19 Pg. 1552-63 (Nov 02 2010) ISSN: 1558-3597 [Electronic] United States
• PMID: 20933357 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Tryptophan
• Arginine
• KIF6 protein, human
• Kinesins

Topics

• Arginine (genetics)
• Case-Control Studies
• Coronary Artery Disease (enzymology, epidemiology, genetics)
• Female
• Genome-Wide Association Study (methods)
• Humans
• Internationality
• Kinesins (genetics)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide (genetics)
• Risk Factors
• Tryptophan (genetics)