Wingrove James A, Daniels Susan E, Sehnert Amy J, Tingley Whittemore, Elashoff Michael R, Rosenberg Steven, Buellesfeld Lutz, Grube Eberhard, Newby L Kristin, Ginsburg Geoffrey S, Kraus William E
CardioDx, Palo Alto, CA, USA.
Circ Cardiovasc Genet. 2008 Oct;1(1):31-8. doi: 10.1161/CIRCGENETICS.108.782730.
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.
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).
Gene expression in peripheral-blood cells reflects the presence and extent of CAD in patients undergoing angiography.
冠状动脉疾病（CAD）的分子病理生理学包括细胞因子释放和血管壁内的局部炎症反应。CAD及其严重程度在循环细胞基因表达中的反映程度尚不清楚。
从最初的冠状动脉导管插入术队列中，我们确定了41例患者，其中包括27例血管造影显示有显著CAD的病例和14例无冠状动脉狭窄的对照。对外周血单核细胞进行全基因组微阵列分析，结果显示病例组和对照组之间有526个基因的差异表达倍数>1.3倍（P<0.05）。对来自同一队列的95例患者（63例病例，32例对照）的独立亚组中的106个基因（50个微阵列最显著基因和另外56个文献报道基因）进行实时聚合酶链反应，结果显示在包括临床和人口统计学因素的多变量分析中，有14个基因（P<0.05）能够独立区分CAD状态。从第二个独立的导管插入术队列中，选择了215例患者进行基于实时聚合酶链反应的重复验证。107例患者（86例病例，21例对照）的病例：对照亚组重复验证了第一个队列中14个多变量显著基因中的11个。对215例患者的整个队列中的14个基因进行分析表明，基因表达与最大冠状动脉狭窄程度成正比（方差分析，P<0.001）。
外周血细胞中的基因表达反映了接受血管造影患者CAD的存在及程度。
