Global DNA methylation mediates the association between urine mono-2-ethylhexyl phthalate and serum apoptotic microparticles in a young Taiwanese population

Abstract

Di-(2-ethylhexyl) phthalate (DEHP) has been used as a plasticizer for decades. Recent research evidence has revealed that environmental factors can alter vascular endothelial cell function through DNA methylation. However, no previous in vitro/vivo study has explored the role of DNA methylation in DEHP exposure and vascular endothelial cell function. In the present study, we enrolled 793 subjects aged 12 to 30 years from a young Taiwanese cohort to investigate the association between mono-2-ethylhexyl phthalate (MEHP) (urine DEHP metabolite), 5mdC/dG (global DNA methylation marker), CD31+/CD42a-, CD31+/CD42a+, and CD14 (apoptotic microparticles of vascular cells). In multiple regression analyses, the levels of mono-2-ethylhexyl phthalate (MEHP) were positively associated with 5mdC/dG and all three apoptotic microparticles. In addition, the regression coefficients between MEHP and the three types of apoptotic microparticles were higher when the 5mdC/dG levels were higher than the 50th percentile. In the structural equation model (SEM), we found that MEHP had a direct correlation with CD31+/CD42a- and an indirect association with CD31+/CD42a- through the effect of 5mdC/dG. Moreover, MEHP only had a direct association with CD31+/CD42a+ and an indirect association with CD14. In conclusion, the results show that global DNA methylation mediates the relationship between MEHP and apoptotic microparticles. These findings indicate that DNA methylation may play a role in the pathogenesis of DEHP-induced endothelial cell apoptosis in humans. Further studies are needed to clarify the causal inference.