Dataset Information

Phthalates and phthalate metabolites in urine from Tianjin and implications for platelet mitochondrial DNA methylation.

ABSTRACT:

Background

Phthalates (PAEs) are important synthetic substances in plastics, attracting much attention due to their potential effects on the cardiovascular system.

Methods

In this study, urine and blood samples from 39 individuals were collected in Tianjin, China. Phthalates and phthalate metabolites (mPAEs) were analyzed using gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography-mass spectrometry (HPLC-MS), respectively. The polymerase chain reaction (PCR) products from bisulfite-treated mitochondrial DNA (mtDNA) samples were analyzed using pyrosequencing technology.

Results

The detection frequencies for 9 PAEs varied from 2.56 to 92.31%, and those for 10 mPAEs varied from 30.77 to 100%. The estimated daily intakes (EDIs) and cumulative risk of PAEs were calculated based on the experimental statistics of urinary PAEs and mPAEs. For PAEs, the HI_RfD (hazard index corresponding to reference doses) values of 10.26% of participants and the HI_TDI (hazard index corresponding to tolerable daily intake) values of 30.77% of participants were estimated to exceed 1, suggesting a relatively high exposure risk. The mtDNA methylation levels in the MT-ATP8 and MT-ND5 were observed to be lower than in the MT-ATP6. Mono-ethyl phthalate (MEP) and MT-ATP8 were positively correlated with triglyceride levels (p < 0.05). Based on the association of PAEs, mtDNA methylation, and triglycerides, the mediating role of mtDNA methylation between PAEs and cardiovascular diseases (CVDs) was analyzed in this study, but no mediated effect was observed.

Conclusion

The effects of PAE exposure on cardiovascular diseases (CVDs) should be investigated further.

SUBMITTER: Li W

PROVIDER: S-EPMC10169620 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Phthalates and phthalate metabolites in urine from Tianjin and implications for platelet mitochondrial DNA methylation.

Li Weixia W Guo Liqiong L Fang Junkai J Zhao Lei L Song Shanjun S Fang Tao T Li Chenguang C Wang Lei L Li Penghui P

Frontiers in public health 20230426

<h4>Background</h4>Phthalates (PAEs) are important synthetic substances in plastics, attracting much attention due to their potential effects on the cardiovascular system.<h4>Methods</h4>In this study, urine and blood samples from 39 individuals were collected in Tianjin, China. Phthalates and phthalate metabolites (mPAEs) were analyzed using gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography-mass spectrometry (HPLC-MS), respectively. The polymerase chain rea ...[more]

PMID: 37181721

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Project description:Exposure to phthalates has been shown to impede the human endocrine system, resulting in deleterious effects on pregnant women and their children. Phthalates modify DNA methylation patterns in infant cord blood. We examined the association between prenatal phthalate exposure and DNA methylation patterns in cord blood in a Korean birth cohort. Phthalate levels were measured in 274 maternal urine samples obtained during late pregnancy and 102 neonatal urine samples obtained at birth, and DNA methylation levels were measured in cord blood samples. For each infant in the cohort, associations between CpG methylation and both maternal and neonate phthalate levels were analyzed using linear mixed models. The results were combined with those from a meta-analysis of the levels of phthalates in maternal and neonatal urine samples, which were also analyzed for MEOHP, MEHHP, MnBP, and DEHP. This meta-analysis revealed significant associations between the methylation levels of CpG sites near the CHN2 and CUL3 genes, which were also associated with MEOHP and MnBP in neonatal urine. When the data were stratified by the sex of the infant, MnBP concentration was found to be associated with one CpG site near the OR2A2 and MEGF11 genes in female infants. In contrast, the concentrations of the three maternal phthalates showed no significant association with CpG site methylation. Furthermore, the data identified distinct differentially methylated regions in maternal and neonatal urine samples following exposure to phthalates. The CpGs with methylation levels that were positively associated with phthalate levels (particularly MEOHP and MnBP) were found to be enriched genes and related pathways. These results indicate that prenatal phthalate exposure is significantly associated with DNA methylation at multiple CpG sites. These alterations in DNA methylation may serve as biomarkers of maternal exposure to phthalates in infants and are potential candidates for investigating the mechanisms by which phthalates impact maternal and neonatal health.

Project description:BackgroundThe association between obesity and cardiovascular disease (CVD) is proven, but why some adults with obesity develop CVD while others remain disease-free is poorly understood. Here, we investigated whether mitochondrial DNA (mtDNA) methylation in platelets is altered prior to CVD development in a population of adults with overweight and obesity.MethodsWe devised a nested case-control study of 200 adults with overweight or obesity who were CVD-free at baseline, of whom 84 developed CVD within 5 years, while 116 remained CVD-free. Platelet mtDNA was isolated from plasma samples at baseline, and mtDNA methylation was quantified in mitochondrially encoded cytochrome-C-oxidase I (MT-CO1; nt6797 and nt6807), II (MT-CO2; nt8113 and nt8117), and III (MT-CO3; nt9444 and nt9449); tRNA leucine 1 (MT-TL1; nt3247 and nt3254); D-loop (nt16383); tRNA phenylalanine (MT-TF; nt624); and light-strand-origin-of-replication (MT-OLR; nt5737, nt5740, and nt5743) by bisulfite-pyrosequencing. Logistic regression was used to estimate the contribution of mtDNA methylation to future CVD risk. ROC curve analysis was used to identify the optimal mtDNA methylation threshold for future CVD risk prediction. A model was generated incorporating methylation at three loci (score 0, 1, or 2 according to 0, 1, or 2-3 hypermethylated loci, respectively), adjusted for potential confounders, such as diastolic and systolic blood pressure, fasting blood glucose, and cholesterol ratio. mtDNA methylation at MT-CO1 nt6807 (OR = 1.08, 95% CI 1.02-1.16; P = 0.014), MT-CO3 nt9444 (OR = 1.22, 95% CI 1.02-1.46, P = 0.042), and MT-TL1 nt3254 (OR = 1.30, 95% CI 1.05-1.61, P = 0.008) was higher at baseline in those who developed CVD by follow-up, compared with those who remained CVD-free. Combined use of the three loci significantly enhanced risk prediction, with hazard ratios of 1.38 (95% CI 0.68-2.78) and 2.68 (95% CI 1.41-5.08) for individuals with score 1 or 2, respectively (P = 0.003). Methylation at these sites was independent of conventional CVD risk factors, including inflammation markers, fasting blood glucose concentration, and blood pressure.ConclusionsMethylations of MT-CO1, MT-CO3, and MT-TL1 are, together, strong predictors of future CVD incidence. Since methylation of these mtDNA domains was independent of conventional CVD risk factors, these markers may represent a novel intrinsic predictor of CVD risk in adults with overweight and obesity.

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Dataset Information

Phthalates and phthalate metabolites in urine from Tianjin and implications for platelet mitochondrial DNA methylation.

Background

Methods

Results

Conclusion

Publications

Phthalates and phthalate metabolites in urine from Tianjin and implications for platelet mitochondrial DNA methylation.

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