Messenger RNAs (mRNAs) play an important role in the pathogenesis of coronary artery disease (CAD). We evaluated the association of selected increase in mRNAs from monocytes with the risk of CAD. Chip data (GSE9820) retrieved from Gene Expression Omnibus (GEO) was re-analyzed, and the selected candidate genes, meeting specific conditions, were up-regulated and verified for specific biomarkers of CAD within a prospective cohort study that recruited 194 individuals and subdivided into two groups: group Non-CAD (GN), n = 68 and group CAD (GC), n = 126. The patients in GC were further categorized into three sub-units according to the extent of coronary stenosis shown during coronary angiography, coded as single-vessel stenosis (GC1, n = 53), 2-vessel stenosis (GC2, n = 50), or ≥ 3-vessel stenosis (GC3, n = 23). All candidate mRNAs expressions were analyzed from patients' monocytes with quantitative PCR (q-PCR). Receiver-operating characteristic (ROC) curves and the area under the ROC curves (AUCs) were used to evaluate the mRNAs' feasibility for CAD prediction. AUCs ≥0.8 were accounted as highly specific association with CAD. GBA2, CSTF3, ZNF606 and MPP5 were selected as mRNAs candidates from chip data reanalysis. GBA2 (P = .002) and ZNF606 (P < .001) expressions were significantly increased in GC. ZNF606 showed significant increase after adjusting the risk factors with logistic regression analysis (OR = 3.804, 95% CI: 1.923, 7.798, P < .001), and its expression level was positively correlated with age (β = 0.04 × 10-3, P < .001). The AUCs (and 95% CI) of ZNF606 expression in GC2 and GC3 were ≥0.8. These findings suggest that it is novel and specific for the association of ZNF606 gene expression from monocytes with the risk of CAD, especially in patients with multiple coronary artery stenosis. Copyright © 2018. Published by Elsevier Inc.