Circulation. 2001;104:2641-2644
Published online before print October 29, 2001, doi: 10.1161/hc4701.100910
Published online before print October 29, 2001, doi: 10.1161/hc4701.100910
(Circulation. 2001;104:2641.)
© 2001 American Heart Association, Inc.
Brief Rapid Communications |
Single Nucleotide Polymorphisms in Multiple Novel Thrombospondin Genes May Be Associated With Familial Premature Myocardial Infarction
From the Cleveland Clinic Foundation, Cleveland, Ohio (E.J.T., D.J.M., R.C., K.K.-M., G.M., E.F.P., O.S.); the Whitehead Institute, MIT Center for Genome Research, Cambridge Mass (S.G., M.F., G.Q.D.); the Massachusetts General Hospital and the National Heart, Lung, and Blood Institute’s Framingham Heart Study, Boston, Mass (C.J.O.); the University of Alabama Medical Center, Birmingham, Ala (W.J.R.); Duke University Medical Center, Durham, NC (L.K.N.); and Millennium Pharmaceuticals, Inc, Cambridge, Mass (J. McCarthy, J. Metivier).
Correspondence to Eric J. Topol, MD, Department of Cardiovascular Medicine, Desk F25, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195. E-mail topole{at}ccf.org
Background— Recent advances in high-throughput genomics technology have expanded our ability to catalogue allelic variants in large sets of candidate genes related to premature coronary artery disease.
Methods and Results— A total of 398 families were identified in 15 participating medical centers; they fulfilled the criteria of myocardial infarction, revascularization, or a significant coronary artery lesion diagnosed before 45 years in men or 50 years in women. A total of 62 vascular biology genes and 72 single-nucleotide polymorphisms were assessed. Previously undescribed variants in 3 related members of the thrombospondin protein family were prominent among a small set of single-nucleotide polymorphisms that showed a statistical association with premature coronary artery disease. A missense variant of thrombospondin 4 (A387P) showed the strongest association, with an adjusted odds ratio for myocardial infarction of 1.89 (P=0.002 adjusted for covariates) for individuals carrying the P allele. A variant in the 3' untranslated region of thrombospondin-2 (change of thymidine to guanine) seemed to have a protective effect against myocardial in individuals homozygous for the variant (adjusted odds ratio of 0.31; P=0.0018). A missense variant in thrombospondin-1 (N700S) was associated with an adjusted odds ratio for coronary artery disease of 11.90 (P=0.041) in homozygous individuals, who also had the lowest level of thrombospondin-1 by plasma assay (P=0.0019).
Conclusions— This large-scale genetic study has identified the potential of multiple novel variants in the thrombospondin gene family to be associated with familial premature myocardial infarction. Notwithstanding multiple caveats, thrombospondins specifically and high-throughput genomic technology in general deserve further study in familial ischemic heart disease.
Key Words: genetics • coronary disease • myocardial infarction • atherosclerosis • genes
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|
|
|
|
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|
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|
|
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|
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|
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|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
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|
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|
|
|
|
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|
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|
|
|
|
|
|
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|
|
|
|
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|
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|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
J J McCarthy, A Parker, R Salem, D J Moliterno, Q Wang, E F Plow, S Rao, G Shen, W J Rogers, L K Newby, et al. Large scale association analysis for identification of genes underlying premature coronary heart disease: cumulative perspective from analysis of 111 candidate genes J. Med. Genet., May 1, 2004; 41(5): 334 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Vassalli and B. R Winkelmann Molecular genetics of myocardial infarction: many genes, more questions than answers Eur. Heart J., March 2, 2004; 25(6): 451 - 453. [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 E. G. Nabel Cardiovascular Disease N. Engl. J. Med., July 3, 2003; 349(1): 60 - 72. [Full Text] [PDF]
|
|
|
|
|
|
O. I. Stenina, I. Krukovets, K. Wang, Z. Zhou, F. Forudi, M. S. Penn, E. J. Topol, and E. F. Plow Increased Expression of Thrombospondin-1 in Vessel Wall of Diabetic Zucker Rat Circulation, July 1, 2003; 107(25): 3209 - 3215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
A. Hamsten and P. Eriksson Thrombospondins and Premature Coronary Artery Disease: Time to Go Beyond Genotype-Phenotype Association Studies Arterioscler Thromb Vasc Biol, January 1, 2003; 23(1): 6 - 7. [Full Text] [PDF]
|
|
|
|
|
|
S. M. Boekholdt, M. D. Trip, R. J.G. Peters, M. Engelen, J. M.A. Boer, E. J.M. Feskens, A. H. Zwinderman, J. J.P. Kastelein, and P. H. Reitsma Thrombospondin-2 Polymorphism Is Associated With a Reduced Risk of Premature Myocardial Infarction Arterioscler Thromb Vasc Biol, December 1, 2002; 22 (12): e24 - e27. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. P. Cannon Evidence-Based Risk Stratification to Target Therapies in Acute Coronary Syndromes Circulation, September 24, 2002; 106(13): 1588 - 1591. [Full Text] [PDF]
|
|
|
|
 |
|
 F.-L. Tan, C. S. Moravec, J. Li, C. Apperson-Hansen, P. M. McCarthy, J. B. Young, and M. Bond The gene expression fingerprint of human heart failure PNAS, August 20, 2002; 99(17): 11387 - 11392. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Tefferi, E. D. Wieben, G. W. Dewald, D. A. H. Whiteman, M. E. Bernard, and T. C. Spelsberg Primer on Medical Genomics Part II: Background Principles and Methods in Molecular Genetics Mayo Clin. Proc., August 1, 2002; 77(8): 785 - 808. [Abstract] [PDF]
|
|
|
|
 |
|
 K.S. MOULTON Plaque Angiogenesis: Its Functions and Regulation Cold Spring Harb Symp Quant Biol, January 1, 2002; 67(0): 471 - 482. [Abstract] [PDF]
|
|