title: Transcriptome analysis in patients with progressive coronary artery disease: identification of differential gene expression in peripheral blood.
abstract: Inflammation as a systemic process plays a central role in atherosclerotic plaque progression (PP). Here we investigated other systemic correlates of PP by global gene expression profiling (GEP) in peripheral blood. From a database of 45,727 coronary angiograms, we identified two patient groups with good risk factor control, but different clinical evolution: First, 16 patients had significant PP leading to repeated coronary interventions, and second, 16 patients had angiographically documented stable courses. GEP revealed 93 differentially expressed genes, of which 23 have unknown function. Among the remaining 70 genes, 10 were associated with progenitor and pluripotent cells, but only three genes with atherosclerosis. We developed a risk prediction gene signature by a multivariable statistical model integrating comprehensive laboratory and clinical patient data. This signature identified PP with high sensitivity and specificity for new patients, as estimated by resampling techniques. GEP results were validated by qPCR for ANK2 and GSTT1.
authors.affiliation: Klinik für Kardiologie und Angiologie II, Universitäts-Herzzentrum Freiburg • Bad Krozingen, Südring 15, 79189, Bad Krozingen, Germany. thomas.nuehrenberg@universitaets-herzzentrum.de
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Nührenberg
authors.forename: Nicole
authors.initials: N
authors.lastname: Langwieser
authors.forename: Harald
authors.initials: H
authors.lastname: Binder
authors.forename: Thorsten
authors.initials: T
authors.lastname: Kurz
authors.forename: Christian
authors.initials: C
authors.lastname: Stratz
authors.forename: Rolf-Peter
authors.initials: RP
authors.lastname: Kienzle
authors.forename: Dietmar
authors.initials: D
authors.lastname: Trenk
authors.forename: Dietlind
authors.initials: D
authors.lastname: Zohlnhöfer-Momm
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Neumann
mesh_terms: D000368:Aged; D017487:Ankyrins / Q000235:genetics; D016000:Cluster Analysis; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000473:pathology; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results; D012307:Risk Factors
chemical_list: C498994:ANK2 protein, human; D017487:Ankyrins; D005819:Genetic Markers; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase