title: Correlation of peripheral-blood gene expression with the extent of coronary artery stenosis.
abstract: BACKGROUND
  The molecular pathophysiology of coronary artery disease (CAD) includes cytokine release and a localized inflammatory response within the vessel wall. The extent to which CAD and its severity is reflected by gene expression in circulating cells is unknown.
  
  
  RESULTS
  From an initial coronary catheterization cohort we identified 41 patients, comprising 27 cases with angiographically significant CAD and 14 controls without coronary stenosis. Whole-genome microarray analysis performed on peripheral-blood mononuclear cells yielded 526 genes with >1.3-fold differential expression (P<0.05) between cases and controls. Real-time polymerase chain reaction on 106 genes (the 50 most significant microarray genes and 56 additional literature genes) in an independent subset of 95 patients (63 cases, 32 controls) from the same cohort yielded 14 genes (P<0.05) that independently discriminated CAD state in a multivariable analysis that included clinical and demographic factors. From an independent second catheterization cohort, 215 patients were selected for real-time polymerase chain reaction-based replication. A case:control subset of 107 patients (86 cases, 21 controls) replicated 11 of the 14 multivariably significant genes from the first cohort. An analysis of the 14 genes in the entire set of 215 patients demonstrated that gene expression was proportional to maximal coronary artery stenosis (P<0.001 by ANOVA).
  
  
  CONCLUSIONS
  Gene expression in peripheral-blood cells reflects the presence and extent of CAD in patients undergoing angiography.
authors.affiliation: CardioDx, Palo Alto, CA, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Wingrove
authors.forename: Susan E
authors.initials: SE
authors.lastname: Daniels
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Sehnert
authors.forename: Whittemore
authors.initials: W
authors.lastname: Tingley
authors.forename: Michael R
authors.initials: MR
authors.lastname: Elashoff
authors.forename: Steven
authors.initials: S
authors.lastname: Rosenberg
authors.forename: Lutz
authors.initials: L
authors.lastname: Buellesfeld
authors.forename: Eberhard
authors.initials: E
authors.lastname: Grube
authors.forename: L Kristin
authors.initials: LK
authors.lastname: Newby
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Ginsburg
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015331:Cohort Studies; D023921:Coronary Stenosis / Q000097:blood* / Q000235:genetics*; D003710:Demography; D005260:Female; D005786:Gene Expression Regulation; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D009657:North Carolina; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction