Objective: For early detection of atherosclerosis(AS),we investigated DNA methylation of AS patients and matched controls in peripheral blood in order to establish a biomarker panel potentially useful for early detection of AS.Methods and results: AS patients and matched controls(50 and 50)were recruited for peripheral blood DNA methylation analyses at the 12 genes promoter loci using nested methylation specific PCR(NT-MSP)in a test set.Based on the test set we determined the promoter methylation of TIMP-1,ABCA1,and ACAT1 as candidate biomarkers with the best sensitivity of 88%and specificity of 90%.In an independent validation set(n=100)we validated the candidate biomarkers for further use in early AS detection.In the validation set combined TIMP-1,ABCA1,and ACAT1 methylation achieved sensitivity of 88%and a specificity of 70%,with coincidence rate of 76%,respectively.Conclusions: In this first pilot study,DNA methylation patterns change significantly in AS patients and AS-related genes in peripheral blood cells.AS-specific methylation of the three-gene panel(TIMP-1,ABCA1,and ACAT1)might be a valuable biomarker for the early detection of AS.