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E-GEOD-12288 - Gene expression patterns in peripheral blood correlate with the extent of coronary artery disease
Released on 31 October 2008, last updated on 27 March 2012
Gene expression profile in circulating leukocytes identifies patients with coronary artery disease Peter Sinnaeve, Mark Donahue, Peter Grass, Jacky Vonderscher, David Seo, Pascal Goldschmidt, Christopher Granger Department of Medicine, Duke University, Durham, NC, USA, Novartis Institute for Biomedical Research, Cambridge, Boston, MA, USA Introduction Systemic and local inflammation plays a prominent pathogenetic role in atherosclerotic coronary artery disease (CAD), but the relationship of phenotypic changes in circulating leukocytes and extent of CAD remains unclear. We have investigated whether gene expression patterns in circulating leukocytes are associated with presence and extent of CAD. Methods Patients undergoing coronary angiography were selected according to their Duke CAD index (CADi), a validated angiographical measure of the extent of coronary atherosclerosis that correlates with outcome. RNA was extracted from 110 patients with CAD (CADi>23) and from 112 partially matched controls without CAD (CADi=0). Gene expression was assessed using Affymetrix U133A chips. Genes correlating with CAD were identified using Spearman’s rank correlation, and predictive gene expression patterns were identified using a partial least squares (PLS) regression analysis. Results 160 individual genes were found to significantly correlate with CADi (rho>0.2, P<0.0027), although changes in individual gene expression were relatively small (1.2 to 1.5 fold). Using these 160 genes, the PLS multivariate regression resulted in a highly predictive model (r2=0.764, P<0.001). Cross-validation showed that most of the predictive model was carried by only 8 genes (r2=0.752) (table 1). Conclusion Simultaneous expression pattern of 8 genes appears to be highly predictive for CAD. Peripheral leukocyte gene expression pattern could be a novel non-invasive biomarker for CAD and lead to new pathophysiologic insights. parallel group design
transcription profiling by array
Peter Grass <firstname.lastname@example.org>, Peter Sinnaeve
Gene expression patterns in peripheral blood correlate with the extent of coronary artery disease. Sinnaeve PR, Donahue MP, Grass P, Seo D, Vonderscher J, Chibout SD, Kraus WE, Sketch M Jr, Nelson C, Ginsburg GS, Goldschmidt-Clermont PJ, Granger CB. , PMID:19750006