Plasma PFOA and PFOS Levels, DNA Methylation, and Blood Lipid Levels: A Pilot Study,Environmental Science & Technology

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Plasma PFOA and PFOS Levels, DNA Methylation, and Blood Lipid Levels: A Pilot Study
Environmental Science & Technology ( IF 10.8 ) Pub Date : 2022-11-14 , DOI: 10.1021/acs.est.2c04107
Xu Cheng ₁ , Yue Wei _{1,

2} , Zefang Zhang ₁ , Fei Wang _{1,

2} , Jia He ₁ , Ruixin Wang ₁ , Yali Xu ₁ , Mulatibieke Keerman ₁ , Shiyang Zhang ₁ , Ying Zhang ₁ , Jiao Bi ₁ , Jinqiu Yao ₁ , Meian He ₁

Affiliation

Exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) is associated with blood lipids in adults, but the underlying mechanisms remain unclear. This pilot study aimed to investigate the associations between PFOA or PFOS and epigenome-wide DNA methylation and assess the mediating effect of DNA methylation on the PFOA/PFOS-blood lipid association. We measured plasma PFOA/PFOS and leukocyte DNA methylation in 98 patients enrolled from the hospital between October 2018 and August 2019. The median plasma PFOA/PFOS levels were 0.85 and 2.29 ng/mL. Plasma PFOA and PFOS levels were significantly associated with elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) levels. There were 63/87 CpG positions and 8/11 differentially methylated regions (DMRs) associated with plasma PFOA/PFOS levels, respectively. In addition, 5 CpG positions (annotated to AFF3, CREB5, NRG2, USF2, and intergenic region) and one DMR annotated to IRF6 may mediate the association between plasma PFOA/PFOS and LDL levels (mediated proportion from 7.29 to 46.77%); two CpG positions may mediate the association between plasma PFOA/PFOS and TC levels (annotated to CREB5 and USF2, mediated proportion is around 30%). The data suggest that PFOA/PFOS exposure alters DNA methylation. More importantly, the association of PFOA/PFOS with lipid indicators was partly mediated by DNA methylation changes in lipid metabolism-related genes.

中文翻译：

血浆 PFOA 和 PFOS 水平、DNA 甲基化和血脂水平：初步研究

暴露于全氟辛酸 (PFOA) 和全氟辛烷磺酸 (PFOS) 与成人血脂有关，但其潜在机制仍不清楚。该试点研究旨在调查 PFOA 或 PFOS 与表观基因组范围内的 DNA 甲基化之间的关联，并评估 DNA 甲基化对 PFOA/PFOS-血脂关联的中介作用。我们测量了 2018 年 10 月至 2019 年 8 月期间从医院入组的 98 名患者的血浆 PFOA/PFOS 和白细胞 DNA 甲基化。血浆 PFOA/PFOS 水平中位数分别为 0.85 和 2.29 ng/mL。血浆 PFOA 和 PFOS 水平与升高的总胆固醇 (TC) 和低密度脂蛋白胆固醇 (LDL) 水平显着相关。分别有 63/87 个 CpG 位置和 8/11 个差异甲基化区域 (DMR) 与血浆 PFOA/PFOS 水平相关。AFF3、CREB5、NRG2、USF2和基因间区域）和一个注释到IRF6的 DMR可能介导血浆 PFOA/PFOS 和 LDL 水平之间的关联（介导比例从 7.29 到 46.77%）；两个 CpG 位置可能介导血浆 PFOA/PFOS 和 TC 水平之间的关联（注释为CREB5和USF2，介导比例约为 30%）。数据表明 PFOA/PFOS 暴露会改变 DNA 甲基化。更重要的是，PFOA/PFOS 与脂质指标的关联部分是由脂质代谢相关基因的 DNA 甲基化变化介导的。

更新日期：2022-11-14

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