Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
Environ Int. 2013 Sep;59:456-61. doi: 10.1016/j.envint.2013.07.008. Epub 2013 Aug 9.
Dioxin exposure has experimentally been associated with changes in DNA methylation, an epigenetic change that is associated with disease. The present study aims to investigate if serum levels of dioxin and other persistent environmental pollutants are related to global DNA methylation in a human sample. In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (all aged 70), global DNA methylation was measured by the Luminometric Methylation Assay in 524 subjects. Twenty-three different POPs, including 16 PCBs, five pesticides, one dioxin (OCDD) and one brominated flame retardant (BDE47) were analysed by HRGC/HRMS. Ten single nucleotide polymorphisms (SNPs) in the Aryl hydrocarbon (Ah)-receptor were analysed by mini-sequencing. High levels of toxic equivalency (TEQ) for PCBs and dioxin were associated with DNA hypermethylation (p=0.030). This was mainly attributed to coplanar non-ortho PCBs. While no significant associations were found between DNA methylation and SNPs in the Ah-receptor, an interaction was found between the SNP rs2237297 and TEQ so that TEQ was associated with hypermethylation (p=0.009) only in subjects with one G-allele (n=103). Also high levels of the PCB126 congener, the OCDD, and the pesticide metabolite p,p'-DDE were related to DNA hypermethylation (p=0.01, 0.03 and 0.003, respectively). In conclusion, in a sample of elderly subjects, high TEQ including PCBs and the dioxin OCDD and high serum levels of PCB126, OCDD, and p,p'-DDE were related to global DNA hypermethylation in a cross-sectional analysis.
二恶英暴露已在实验中与 DNA 甲基化的变化相关联，这是一种与疾病相关的表观遗传变化。本研究旨在调查人体样本中二恶英和其他持久性环境污染物的血清水平是否与全球 DNA 甲基化相关。在基于人群的乌普萨拉老年人血管前瞻性研究（PIVUS）中（所有年龄均为 70 岁），在 524 名受试者中通过发光甲基化测定法测量了全球 DNA 甲基化。通过高分辨气相色谱/高分辨质谱分析了 23 种不同的持久性有机污染物（POPs），包括 16 种多氯联苯、5 种农药、1 种二恶英（OCDD）和 1 种溴化阻燃剂（BDE47）。通过小型测序分析了芳烃受体中的 10 个单核苷酸多态性（SNP）。高水平的多氯联苯和二恶英的毒性等效值（TEQ）与 DNA 超甲基化相关（p=0.030）。这主要归因于共平面非邻位多氯联苯。虽然在 Ah 受体中的 SNP 与 DNA 甲基化之间未发现显著相关性，但在 SNP rs2237297 与 TEQ 之间发现了相互作用，因此仅在具有 1 个 G 等位基因的受试者中（n=103），TEQ 与超甲基化相关（p=0.009）。同样，高浓度的多氯联苯 126 同系物、二恶英 OCDD 和农药代谢物 p,p'-DDE 也与 DNA 超甲基化相关（p=0.01、0.03 和 0.003）。总之，在老年受试者样本中，高 TEQ（包括多氯联苯和二恶英 OCDD）和高血清水平的多氯联苯 126、二恶英 OCDD 和 p,p'-DDE 与横断面分析中的全球 DNA 超甲基化相关。
