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

Clin Epigenetics. 2023 May 17;15(1):87. doi: 10.1186/s13148-023-01502-z.

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 12-30 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 study found that the inverse relationship between MEHP and adiponectin was stronger when levels of 5mdC/dG were above the median. This was supported by differential unstandardized regression coefficients (- 0.095 vs. - 0.049, P value for interaction = 0.038)). Subgroup analysis also showed a negative correlation between MEHP and adiponectin in individuals with the I/I ACE genotype, but not in those with other genotypes, although the P value for interaction was borderline significant (0.06). The structural equation model analysis indicated that MEHP has a direct inverse effect on adiponectin and an indirect effect via 5mdC/dG.

Conclusions: In this young Taiwanese population, our findings suggest that urine MEHP levels are negatively correlated with serum adiponectin levels, and epigenetic modifications may play a role in this association. Further study is needed to validate these results and determine causality.

Keywords: 5mdC/dG; Adiponectin; DEHP (di-(2-ethylhexyl) phthalate); Epigenetic modifications; Glucose homeostasis; MEHP (mono(2-ethylhexyl) phthalate).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / genetics
  • Adiponectin / metabolism
  • DNA Methylation
  • Diethylhexyl Phthalate* / analysis
  • Diethylhexyl Phthalate* / metabolism
  • Humans
  • Peptidyl-Dipeptidase A* / genetics
  • Peptidyl-Dipeptidase A* / metabolism
  • Taiwan

Substances

  • Adiponectin
  • Diethylhexyl Phthalate
  • mono-(2-ethylhexyl)phthalate
  • Peptidyl-Dipeptidase A
  • phthalic acid
  • ACE protein, human