The association between urine di-(2-ethylhexyl) phthalate metabolites, global DNA methylation, and subclinical atherosclerosis in a young Taiwanese population.

Di-(2-ethylhexyl) phthalate (DEHP) has been utilized in many products for years. DEHP exposure has been linked to cardiovascular diseases (CVD) and its risk factors. Recent evidence has found a crucial role for epigenetics, including DNA methylation, in CVD. Moreover, DEHP exposure has proved to alter DNA methylation in epidemiological studies. However, the interplay between DEHP exposure, global DNA methylation, and atherosclerosis has never been reported. In this current study, we enrolled 793 participants (12-30 years) from a Taiwanese population to investigate the association between concentrations of DEHP metabolites, 5mdC/dG (global DNA methylation marker) and the carotid intima-media thickness (CIMT). The results showed urine mono-2-ethylhexyl phthalate (MEHP) level was positively correlated with 5mdC/dG and CIMT, respectively. In logistic regression models, the odds ratios (OR) of thicker CIMT (greater than 75th percentile) with one unit increase in ln-MEHP level was higher when levels of 5mdC/dG were above 50%. In structural equation model, the result showed urine MEHP levels are directly associated with CIMT. Moreover, MEHP had an indirect association with CIMT through the 5mdC/dG after adjusting other confounding effects. In the current study, urine DEHP metabolite levels were positively correlated with 5mdC/dG, and CIMT. Our results showed DEHP had a direct and indirect association with CIMT through the 5mdC/dG. The finding implies that DNA methylation may mediate the association between DEHP exposures and subclinical atherosclerosis in this young population. Future effort is needed to elucidate the causal relationship between DEHP exposure, DNA methylation and CVD.