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Identification of new genes differentially expressed in coronary artery disease by expression profiling

¹ Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland 44115
² Center for Molecular Genetics, Cleveland Clinic Foundation, Cleveland, Ohio 44195
³ Department of Molecular Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195
⁴ Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, Ohio 44195

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 nonatherosclerotic 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, GST, encoding a reducing agent, showed downregulated 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, ß2-arrestin, membrane aminopeptidase, cathepsins K and H, MIR-7, TNF--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.

array; atherosclerosis; coronary artery disease/myocardial infarction; gene expression; sudden death

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