The role of angiotensin I-converting enzyme gene polymorphism and global DNA methylation in the negative associations between urine di-(2-ethylhexyl) phthalate metabolites and serum adiponectin in a young Taiwanese population

Abstract

Background Adiponectin is a key protein produced in adipose tissue, with crucial involvement in multiple metabolic processes. Di-(2-ethylhexyl) phthalate (DEHP), one of the phthalate compounds used as a plasticizer, has been shown to decrease adiponectin levels in vitro and in vivo studies. However, the role of angiotensin I-converting enzyme (ACE) gene polymorphism and epigenetic changes in the relationship between DEHP exposure and adiponectin levels is not well understood. Methods This study examined the correlation between urine levels of DEHP metabolite, epigenetic marker 5mdC/dG, ACE gene phenotypes, and adiponectin levels in a sample of 699 individuals aged 12 to 30 from Taiwan. Results Results showed a positive relationship between mono-2-ethylhexyl phthalate (MEHP) and 5mdC/dG, and a negative association between both MEHP and 5mdC/dG with adiponectin. The inverse relationship between MEHP and adiponectin was stronger when 5mdC/dG levels were above the median, as indicated by a smaller regression coefficient (-0.095 compared to -0.049). The structural equation model (SEM) analysis indicated that MEHP has a direct inverse effect on adiponectin and an indirect effect via 5mdC/dG. Subgroup analysis revealed a negative correlation between MEHP and adiponectin in individuals with the I/I ACE genotype, but not in others. Conclusions In this young Taiwanese population, our findings suggest that urine MEHP levels are negatively correlated with serum adiponectin levels and that ACE gene polymorphism and epigenetic modifications may play a role in this association. Further study is needed to validate these results and determine causality.