The sex-specific association of phthalate exposure with DNA methylation and characteristics of body fat in children

The present study assessed the association between phthalate exposure and mitochondrial DNA (mtDNA) polymerase γ (POLG) methylation along with the potential effect on the characteristics of body fat in children. A total of 152 children were enrolled. The urinary concentrations of phthalate metabolites were measured using ultraperformance liquid chromatography-tandem mass spectrometry. Genomic DNA was extracted from the buffy coat, and bisulfite-treated DNA was subjected to a pyrosequencing assay. In total, 17 CpG sites in the exon 2 region of POLG were included in the analysis. A multivariable regression model was applied to determine whether characteristics of body fat were associated with phthalate exposure and methylation of POLG. After adjustment for covariates, male children with a ten-fold increase in mono-methyl phthalate (MMP) or mono-benzyl phthalate (MBzP) concentrations had significantly higher measurements for total body fat (MMP: β = 6.47%; MBzP: β = 3.54%), and trunk fat (MMP: β = 6.67%; MBzP: β = 3.90%). Male children who had hypermethylation at the 2nd CpG site in exon 2 of POLG also had high measurements for BMI (β = 1.66 kg/m2), waist (β = 4.49 cm) and hip (β = 4.81 cm) circumference, total body fat (β = 5.48%), and trunk fat (β = 6.21%). A dose-response relationship existed between methylation at the 2nd CpG site in exon 2 of POLG and characteristics of body fat (p for trend<0.01). This study suggested that male children who are exposed to phthalic acid esters have high body weight, BMI, and body and trunk fat percentages. Methylation of the exon 2 region of POLG is a possible mechanism behind the causal effect of endocrine-disrupting substances.