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

Chien-Yu Lin, Ching-Way Chen, Hui-Ling Lee, Charlene Wu, Chikang Wang, Fung-Chang Sung, Ta-Chen Su

Journal: The Science of the total environment 2022;808():152054

PMID: 34863772

Full Text on Elsevier Science View on PubMed

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.

Address: Department of Internal Medicine, En Chu Kong Hospital, New Taipei City 237, Taiwan; School of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan; Department of Environmental Engineering and Health, Yuanpei University of Medical Technology, Hsinchu 300, Taiwan.; Department of Cardiology, National Taiwan University Hospital Yunlin Branch, Taiwan.; Department of Chemistry, Fu Jen Catholic University, New Taipei City 242, Taiwan.; Global Health, National Taiwan University Hospital, Taipei 100, Taiwan.; Department of Environmental Engineering and Health, Yuanpei University of Medical Technology, Hsinchu 300, Taiwan.; Department of Health Services Administration, College of Public Health, China Medical University, Taichung 404, Taiwan.; Department of Environmental and Occupational Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan; Department of Internal Medicine and Cardiovascular Center, National Taiwan University Hospital, Taipei 10002, Taiwan; Institute of Environmental and Occupational Health Sciences, College of Public Health, National Taiwan University, Taipei 10002, Taiwan; The Experimental Forest, National Taiwan University, Nantou 558, Taiwan. Electronic address: [email protected].

DOI: 10.1016/j.scitotenv.2021.152054

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MeSH Terms: DNA Methylation, Diethylhexyl Phthalate, Humans, Phthalic Acids