This Article Full Text Full Text (PDF) All Versions of this Article: 22/5/874    most recent 01.ATV.0000016258.40568.F1v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Harrap, S. B. Articles by Anderson, S. T. Search for Related Content PubMed PubMed Citation Articles by Harrap, S. B. Articles by Anderson, S. T. Related Collections Clinical genetics Genomics Acute coronary syndromes Acute myocardial infarction Genetics of cardiovascular disease

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:874.)
© 2002 American Heart Association, Inc.

Thrombosis

Genome-Wide Linkage Analysis of the Acute Coronary Syndrome Suggests a Locus on Chromosome 2

Stephen B. Harrap; Kim S. Zammit; Zilla Y.H. Wong; Fiona M. Williams; Melanie Bahlo; Andrew M. Tonkin; Stanley T. Anderson

From the Department of Physiology (S.B.H., K.S.Z., Z.Y.H.W., F.M.W.), The University of Melbourne, and the Walter and Eliza Hall Medical Research Institute (M.B.), Parkville, Victoria, Australia; Austin and Repatriation Medical Centre (A.M.T.), Heidelberg, Victoria, Australia; and Alfred Hospital (S.T.A.), Prahran, Victoria, Australia.

Correspondence to Prof Stephen Harrap, Department of Physiology, The University of Melbourne, Victoria 3010, Australia. E-mail s.harrap@ physiology.unimelb.edu.au

A positive family history is a recognized cardiovascular risk factor, and genome-wide scans may reveal susceptibility loci for coronary artery disease. The acute coronary syndrome, consisting of myocardial infarction and unstable angina, is the most important manifestation of coronary disease and is characterized by atherosclerotic plaque disruption and coronary thrombosis. From 6000 hospital admissions to cardiology units, we identified affected sibling pairs (n=61) who had documented acute coronary syndrome before the age of 70 years. A 10-cM resolution genetic map and MAPMAKER/SIBS were used for genome-wide linkage analysis. One locus on chromosome 2q36-q37.3 showed linkage with a lod score of 2.63 (P<0.0001). Separate multipoint fine-mapping of this locus with independent markers replicated the linkage results (lod 2.64). Two other regions on chromosomes 3q26-q27 and 20q11-q13 showed lod scores in excess of 1.5 (P<0.005). This genome scan in acute coronary syndrome suggests 1 locus that encompasses the gene encoding the insulin receptor substrate-1 gene. Two other potential loci were identified. These data imply that a limited number of potent susceptibility genes exist for the acute coronary syndrome. Such genes are likely to be relevant to the combined processes of atherosclerosis, plaque instability, and coronary thrombosis.

Key Words: genome scan • coronary disease • mapping • myocardial infarction • insulin receptor substrate-1

This article has been cited by other articles:

				R. Sherva, M. B. Miller, J. S. Pankow, S. C. Hunt, E. Boerwinkle, T. H. Mosley, A. B. Weder, J. D. Curb, A. Luke, A. C. Morrison, et al. A Whole-Genome Scan for Stroke or Myocardial Infarction in Family Blood Pressure Program Families Stroke, April 1, 2008; 39(4): 1115 - 1120. [Abstract] [Full Text] [PDF]

				S. B. Damani and E. J. Topol Future Use of Genomics in Coronary Artery Disease J. Am. Coll. Cardiol., November 13, 2007; 50(20): 1933 - 1940. [Abstract] [Full Text] [PDF]

				D. K. Arnett and for the Writing Group Summary of the American Heart Association's Scientific Statement on the Relevance of Genetics and Genomics for Prevention and Treatment of Cardiovascular Disease Arterioscler. Thromb. Vasc. Biol., August 1, 2007; 27(8): 1682 - 1686. [Full Text] [PDF]

				D. K. Arnett, A. E. Baird, R. A. Barkley, C. T. Basson, E. Boerwinkle, S. K. Ganesh, D. M. Herrington, Y. Hong, C. Jaquish, D. A. McDermott, et al. Relevance of Genetics and Genomics for Prevention and Treatment of Cardiovascular Disease: A Scientific Statement From the American Heart Association Council on Epidemiology and Prevention, the Stroke Council, and the Functional Genomics and Translational Biology Interdisciplinary Working Group Circulation, June 5, 2007; 115(22): 2878 - 2901. [Abstract] [Full Text] [PDF]

				D. T. Miller, P. M. Ridker, P. Libby, and D. J. Kwiatkowski Atherosclerosis: The Path From Genomics to Therapeutics J. Am. Coll. Cardiol., April 17, 2007; 49(15): 1589 - 1599. [Abstract] [Full Text] [PDF]

				A. K Luo, B. K Jefferson, M. J Garcia, G. S Ginsburg, and E. J Topol Challenges in the phenotypic characterisation of patients in genetic studies of coronary artery disease J. Med. Genet., March 1, 2007; 44(3): 161 - 165. [Abstract] [Full Text] [PDF]

				J. C. Cohen Genetic Approaches to Coronary Heart Disease J. Am. Coll. Cardiol., October 27, 2006; 48(9_Suppl_A): A10 - A14. [Abstract] [Full Text] [PDF]

				E. J. Topol, J. Smith, E. F. Plow, and Q. K. Wang Genetic susceptibility to myocardial infarction and coronary artery disease Hum. Mol. Genet., October 15, 2006; 15(suppl_2): R117 - R123. [Abstract] [Full Text] [PDF]

				N. Fiotti, N. Altamura, M. Fisicaro, N. Carraro, L. Uxa, G. Grassi, L. Torelli, R. Gobbato, G. Guarnieri, B. T. Baxter, et al. MMP-9 Microsatellite Polymorphism and Susceptibility to Carotid Arteries Atherosclerosis Arterioscler. Thromb. Vasc. Biol., June 1, 2006; 26(6): 1330 - 1336. [Abstract] [Full Text] [PDF]

				R. S. Vasan Biomarkers of Cardiovascular Disease: Molecular Basis and Practical Considerations Circulation, May 16, 2006; 113(19): 2335 - 2362. [Full Text] [PDF]

				J. M. McCaffery, N. Frasure-Smith, M.-P. Dube, P. Theroux, G. A. Rouleau, Q. Duan, and F. Lesperance Common genetic vulnerability to depressive symptoms and coronary artery disease: a review and development of candidate genes related to inflammation and serotonin. Psychosom Med, March 1, 2006; 68(2): 187 - 200. [Abstract] [Full Text] [PDF]

				G. S. Ginsburg, M. P. Donahue, and L. K. Newby Prospects for Personalized Cardiovascular Medicine: The Impact of Genomics J. Am. Coll. Cardiol., November 1, 2005; 46(9): 1615 - 1627. [Abstract] [Full Text] [PDF]

				E. J. Topol The Genomic Basis of Myocardial Infarction J. Am. Coll. Cardiol., October 18, 2005; 46(8): 1456 - 1465. [Full Text] [PDF]

				T. M. Doherty, L. A. Fitzpatrick, D. Inoue, J.-H. Qiao, M. C. Fishbein, R. C. Detrano, P. K. Shah, and T. B. Rajavashisth Molecular, Endocrine, and Genetic Mechanisms of Arterial Calcification Endocr. Rev., August 1, 2004; 25(4): 629 - 672. [Abstract] [Full Text] [PDF]

				M. Federici, A. Pandolfi, E. A. De Filippis, G. Pellegrini, R. Menghini, D. Lauro, M. Cardellini, M. Romano, G. Sesti, R. Lauro, et al. G972R IRS-1 Variant Impairs Insulin Regulation of Endothelial Nitric Oxide Synthase in Cultured Human Endothelial Cells Circulation, January 27, 2004; 109(3): 399 - 405. [Abstract] [Full Text] [PDF]