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

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 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

J Am Coll Cardiol 2010 Nov;56(19):1552-63

Department of Medicine, Stanford University School of Medicine, Stanford, California 94304-1334, USA.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacc.2010.06.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084526PMC
November 2010
92 Reads

Publication Analysis

Top Keywords

trp719arg polymorphism
16
kif6 trp719arg
12
risk cad
12
polymorphism rs20455
8
risk clinical
8
clinical cad
8
coronary artery
8
carriers 719arg
8
increased risk
8
719arg carriers
8
years age
8
younger years
8
case-control studies
8
artery disease
8
719arg allele
8
cad
6
risk
5
studies demonstrated
4
genotyped studies
4
controls genotyped
4

Similar Publications