Human Molecular Genetics Advance Access originally published online on October 20, 2004
Human Molecular Genetics 2004 13(24):3181-3188; doi:10.1093/hmg/ddh329
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Human Molecular Genetics, Vol. 13, No. 24 © Oxford University Press 2004; all rights reserved
Transcription factor MEF2A mutations in patients with coronary artery disease
1Department of Molecular Cardiology, Lerner Research Institute, 2Center for Cardiovascular Genetics, Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA and 3Department of Biological, Geological and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USA
Received August 25, 2004; Accepted October 11, 2004
Coronary artery disease (CAD), including its most serious complication myocardial infraction (MI), is the leading cause of death in the US and developed countries. We recently discovered that a seven-amino acid deletion in MEF2A, a transcription factor with a high level of expression in the endothelium of coronary arteries, co-segregates with CAD/MI in one family, and it suppresses transcription activation activity of MEF2A by a dominant-negative mechanism. In this study, we used single-strand conformation polymorphism and DNA sequence analyses to identify mutations in MEF2A in 207 independent CAD/MI patients and 191 controls with normal angiograms. We identified three novel mutations in exon 7 of MEF2A in four of 207 CAD/MI patients (1.93%). No mutations were detected in the 191 controls. The mutations identified here include N263S identified in two independent CAD patients, P279L in one patient and his father with the diagnosis of CAD and G283D in one patient. These mutations are clustered within or close to the major transcriptional activation domain of MEF2A. They significantly reduce the transcriptional activation activity of MEF2A and act by a loss-of-function mechanism. The gene carriers with loss-of-function mutations appear to be associated with less severe CAD. These results suggest that CAD/MI can result from a spectrum of MEF2A transcription dysfunctions ranging from loss-of-function to dominant-negative suppression and that a significant percent of the CAD/MI population (1.93%) may carry mutations in MEF2A, although further definition of the prevalence of MEF2A mutations is warranted.
* To whom correspondence should be addressed at: Center for Molecular Genetics/ND4-38, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. Tel: +1 2164450570; Fax: +1 2164442682; Email: wangq2{at}ccf.org
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Fan, P. Ouyang, A. A. Timur, P. He, S.-A. You, Y. Hu, T. Ke, D. J. Driscoll, Q. Chen, and Q. K. Wang Novel Roles of GATA1 in Regulation of Angiogenic Factor AGGF1 and Endothelial Cell Function J. Biol. Chem., August 28, 2009; 284(35): 23331 - 23343. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Guella, V. Rimoldi, R. Asselta, D. Ardissino, M. Francolini, N. Martinelli, D. Girelli, F. Peyvandi, M. Tubaro, P. A. Merlini, et al. Association and Functional Analyses of MEF2A as a Susceptibility Gene for Premature Myocardial Infarction and Coronary Artery Disease Circ Cardiovasc Genet, April 1, 2009; 2(2): 165 - 172. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K. Schnoes, I. Z. Jaffe, L. Iyer, A. Dabreo, M. Aronovitz, B. Newfell, U. Hansen, G. Rosano, and M. E. Mendelsohn Research Resource: Rapid Recruitment of Temporally Distinct Vascular Gene Sets by Estrogen Mol. Endocrinol., November 1, 2008; 22(11): 2544 - 2556. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Gulec, A. Ruchan Akar, and N. Akar MEF2A Sequence Variants in Turkish Population Clinical and Applied Thrombosis/Hemostasis, October 1, 2008; 14(4): 465 - 467. [Abstract] [PDF]
|
|
|
|
 |
|
 W. Lieb, B. Mayer, I. R. Konig, I. Borwitzky, A. Gotz, S. Kain, C. Hengstenberg, P. Linsel-Nitschke, M. Fischer, A. Doring, et al. Lack of Association Between the MEF2A Gene and Myocardial Infarction Circulation, January 15, 2008; 117(2): 185 - 191. [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]
|
|
|
|
 |
|
 Y. Hinits and S. M. Hughes Mef2s are required for thick filament formation in nascent muscle fibres Development, July 1, 2007; 134(13): 2511 - 2519. [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]
|
|
|
|
 |
|
 E. J Topol The genetics of heart attack. Heart, June 1, 2006; 92(6): 855 - 861. [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]
|
|
|
|
|
|
P Gonzalez, M Garcia-Castro, J R Reguero, A Batalla, A G Ordonez, R L Palop, I Lozano, M Montes, V Alvarez, and E Coto The Pro279Leu variant in the transcription factor MEF2A is associated with myocardial infarction J. Med. Genet., February 1, 2006; 43(2): 167 - 169. [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]
|
|