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Physiol. Genomics (August 5, 2003). doi:10.1152/physiolgenomics.00181.2002
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Submitted on December 18, 2002
Accepted on July 24, 2003

Identification of New Genes Differentially Expressed in Coronary Artery Disease by Expression Profiling

Stephen R Archacki1, George Angheloiu2, Xiao-li Tian3, Fen Lai Tan4, Nick DiPaola2, Gong-Qing Shen3, Christine Moravec5, Stephen Ellis2, Eric J Topol3, and Qing Wang6*

1 Department of Biology, Cleveland State University, Cleveland, OH, USA; Center for Molecular Genetics, The Cleveland Clinic Foundation, Cleveland, OH, USA; Department of Molecular Cardiology, The Cleveland Clinic Foundation, Cleveland, OH, USA
2 Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, OH, USA
3 Center for Molecular Genetics, The Cleveland Clinic Foundation, Cleveland, OH, USA; Department of Molecular Cardiology, The Cleveland Clinic Foundation, Cleveland, OH, USA; Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, OH, USA
4 Department of Molecular Cardiology, The Cleveland Clinic Foundation, Cleveland, OH, USA
5 Department of Biology, Cleveland State University, Cleveland, OH, USA; Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, OH, USA
6 Department of Biology, Cleveland State University, Cleveland, OH, USA; Center for Molecular Genetics, The Cleveland Clinic Foundation, Cleveland, OH, USA; Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, OH, USA

* To whom correspondence should be addressed. E-mail: wangq2{at}ccf.org.

Genetic factors increase the risk to coronary artery disease (CAD). To date, a limited number of genes that potentially contribute to development of CAD have been identified. In this study, we have performed large-scale gene expression analysis of ~12,000 human genes in nine severely atherosclerotic and six non-atherosclerotic human coronary arteries using oligonucleotide microarrays. Fifty-six genes showed differential expression in atherosclerotic coronary artery tissues; expression of 55 genes was increased in atherosclerotic coronary arteries, whereas only one gene, glutathione-S-transferase gene encoding a reducing agent, showed down-regulated expression. The expression data of selected genes were validated by quantitative RT-PCR analysis as well as immunostaining. The associations of 49 genes with CAD appear to be novel and they include genes encoding ICAM-2, PIM-2, ECGF1, fusin, B cell activator (BL34, GOS8), Rho GTPase activating protein-4, retinoic acid receptor responder, {beta}2-arrestin, membrane aminopeptidase, cathepsin K and H, MIR-7, TNF {alpha}-induced protein 2 (B94), and flavocytochrome 558. In conclusion, we have identified 56 genes whose expression is associated with CAD, and 49 of them may represent new genes linked to CAD.




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