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

• Published in: Journal of the American College of Cardiology Vol. 56; no. 19; pp. 1552 - 1563
• Main Authors: Assimes, Themistocles L., MD, PhD, Hólm, Hilma, MD, Reilly, Muredach P., MB, Thorleifsson, Gudmar, PhD, Voight, Benjamin F., PhD, Erdmann, Jeanette, PhD, Willenborg, Christina, MSc, Vaidya, Dhananjay, MBBS, PhD, MPH, Xie, Changchun, PhD, Patterson, Chris C., PhD, Morgan, Thomas M., MD, Burnett, Mary Susan, PhD, Li, Mingyao, PhD, Thompson, John R., PhD, Absher, Devin, PhD, Iribarren, Carlos, MD, MPH, PhD, Go, Alan, MD, Sidney, Stephen, MD, MPH, Risch, Neil, PhD, Tang, Hua, PhD, Myers, Richard M., PhD, Berger, Klaus, MD, Stoll, Monika, PhD, Shah, Svati H., MD, MHS, Thorgeirsson, Gudmundur, MD, PhD, Andersen, Karl, MD, PhD, Havulinna, Aki S., MSc, Herrera, J. Enrique, MS, Mathias, Rasika A., ScD, Ruczinski, Ingo, PhD, Suktitipat, Bhoom, MD, Yanek, Lisa R., MPH, Becker, Lewis C., MD, Linsel-Nitschke, Patrick, MD, Lieb, Wolfgang, MD, Hengstenberg, Christian, MD, Stark, Klaus, PhD, Reinhard, Wibke, MD, Winogradow, Janina, MD, Grosshennig, Anika, MSc, Schreiber, Stefan, MD, Wichmann, H.-Erich, MD, Meisinger, Christa, MD, MPH, Yee, Jean, BS, Friedlander, Yechiel, PhD, Meigs, James B., MD, MPH, Williams, Gordon, MD, Nathan, David M., MD, MacRae, Calum A., MD, PhD, Qu, Liming, MS, Wilensky, Robert L., MD, Matthai, William H., MD, Qasim, Atif N., MD, Hakonarson, Hakon, MD, PhD, Pichard, Augusto D., MD, Kent, Kenneth M., MD, PhD, Satler, Lowell, MD, Waksman, Ron, MD, Knouff, Christopher W., MD, PhD, Waterworth, Dawn M., PhD, Walker, Max C., BSc, Marrugat, Jaume, MD, PhD, Lucas, Gavin, PhD, Subirana, Isaac, MSc, Sala, Joan, MD, Martinelli, Nicola, MD, Olivieri, Oliviero, MD, Trabetti, Elisabetta, PhD, Malerba, Giovanni, PhD, Pignatti, Pier Franco, MD, Guiducci, Candace, BS, Mirel, Daniel, PhD, Parkin, Melissa, BS, Asselta, Rosanna, PhD, Duga, Stefano, PhD, Musunuru, Kiran, MD, PhD, MPH, Daly, Mark J., PhD, Purcell, Shaun, PhD, Wright, Benjamin J., PhD, Ball, Stephen G., PhD, Deloukas, Panos, PhD, Scholz, Michael, Cambien, Francois, MD, Huge, Andreas, PhD, Scheffold, Thomas, PhD, Granger, Christopher B., MD, Peltonen, Leena, MD, PhD, McKeown, Pascal P., MD, Altshuler, David, MD, PhD, Devaney, Joseph M., PhD, Epstein, Stephen E., MD, Engert, James C., PhD, Anand, Sonia S., MD, PhD, Hall, Alistair S., MD, Ziegler, Andreas, PhD, O'Donnell, Christopher J., MD, MPH, Spertus, John A., MD, MPh, Siscovick, David, MD, MPH, Thorsteinsdottir, Unnur, PhD, Schunkert, Heribert, MD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 02-11-2010; Elsevier; Elsevier Limited
• Subjects: African Americans; Age; Arginine - genetics; Atherosclerosis; Biological and medical sciences; Cardiac and Cardiovascular Systems; Cardiology; Cardiology. Vascular system; Cardiovascular; Cardiovascular disease; Case-Control Studies; Clinical Medicine; Confidence intervals; Consortia; coronary artery disease; Coronary Artery Disease - enzymology; Coronary Artery Disease - epidemiology; Coronary Artery Disease - genetics; Coronary heart disease; Female; Genome-Wide Association Study - methods; Genomes; Heart; Heart attacks; Hispanic people; Humans; infarction; Internal Medicine; International organizations; Internationality; Ischemia; Kardiologi; KIF6; kinesin-like protein 6; Kinesins - genetics; Klinisk medicin; Male; Medical and Health Sciences; Medical research; Medical sciences; Medicin och hälsovetenskap; Middle Aged; myocardial; myocardial infarction; polymorphism; Polymorphism, Single Nucleotide - genetics; Proteins; Risk Factors; Studies; Tryptophan - genetics; Womens health; coronary artery disease; OR; single nucleotide polymorphism; CI; myocardial infarction; CAD; polymorphism; HR; odds ratio; KIF6; SNP; kinesin-like protein 6; hazard ratio; confidence interval; MI; Association; Cardiovascular disease; Circulatory system; Case control study; Cardiology; Coronary heart disease; Protein; Polymorphism
• ISSN: 0735-1097; 1558-3597; 1558-3597
• DOI: 10.1016/j.jacc.2010.06.022

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.