Genome-wide association studies have revealed an association between the genetic variant rs17514846 in theFURINgene and coronary artery disease. We investigated the mechanism through which rs17514846 modulatesFURINexpression. An analysis of isogenic monocytic cell lines showed that the cells of the rs17514846 A/A genotype expressed higher levels ofFURINthan cells of the C/C genotype. Pyrosequencing showed that the cytosine (in a CpG motif) at the rs17514846 position on the C allele was methylated. Treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine increasedFURINexpression. An electrophoretic mobility super-shift assay with a probe corresponding to the DNA sequence at and around the rs17514846 position of the C allele detected DNA-protein complex bands that were altered by an anti-MeCP2 antibody. A chromatin immunoprecipitation assay with the anti-MeCP2 antibody showed an enrichment of the DNA sequence containing the rs17514846 site. siRNA-mediated knockdown of MeCP2 caused an increase in FURIN expression. Furthermore, MeCP2 knockdown increased monocyte migration and proliferation, and this effect was diminished by a FURIN inhibitor. The results of our study suggest that DNA methylation inhibitsFURINexpression and that the coronary artery disease-predisposing variant rs17514846 modulatesFURINexpression and monocyte migration via an allele-specific effect on DNA methylation.