The top two CpG sites, cg24908166 and cg12324353, are located within TERT (telomerase reverse transcriptase). High levels of TERT expression are found in macrophages of human atherosclerotic lesions [10]. Two other CpG sites, cg09397246 and cg26405020, were located near the transcription start site of FES (FES proto-oncogene, tyrosine kinase), which has been identified by GWAS to be associated with blood pressure and hypertension [11]. Smoking was further associated with methylation of cg09469355 and cg05603985 within SKI (avian sarcoma viral oncogene homolog) which is a repressor of TGF-beta activity. Decreased TGF-beta activity is associated with atherosclerosis development and plaque instability [12, 13]. This could be a plausible pathway through which smoking can increase the occurrence of CAD since smoking has already been associated with decreased plasma levels of TGF-beta and decreased expression of TGF-beta in bronchial cell lines [14, 15].
