Cigarette smoking related DNA methylation in peripheral leukocytes and cardiovascular risk in young adults.

There is strong evidence linking changes in DNA methylation with cigarette smoking, and smoking has long been associated with cardiovascular disease; however not many studies have investigated the effects of smoking related DNA methylation changes on cardiovascular risk, especially in young adults. We explored this relationship in 480 African American and European American men and women aged 27.3 ± 3.5. Out of the DNA methylation data obtained from Illumina 450 k in peripheral leukocytes, 62 CpG sites that have been associated with smoking in multiple studies were selected. Of these, 48 were significantly related to smoking within our population. These CpG sites were then used to predict 2 subclinical markers of cardiovascular health: carotid intima media thickness and left ventricular mass (LVM). There was a significant association (FDR < 0.05) between LVM and 13 of these CpG sites. We constructed a DNA methylation score using these CpG sites and found a significant association between this score and LVM (p < 0.01). Mediation test showed that 36.5% of the effect of smoking on LVM could be explained by this methylation score. Our data suggests that, in young adult populations, cigarette smoking related DNA methylation changes are already associated with changes in subclinical markers of cardiovascular health.