Hokkaido University Center for Environmental and Health Sciences, Sapporo, Japan.
National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
Environ Int. 2018 Jun;115:21-28. doi: 10.1016/j.envint.2018.03.004. Epub 2018 Mar 12.
Prenatal exposure to perfluoroalkyl substances (PFASs) influences fetal development and later in life.
To investigate cord blood DNA methylation changes associated with prenatal exposure to PFASs.
We assessed DNA methylation in cord blood samples from 190 mother-child pairs from the Sapporo cohort of the Hokkaido Study (discovery cohort) and from 37 mother-child pairs from the Taiwan Maternal and Infant Cohort Study (replication cohort) using the Illumina HumanMethylation 450 BeadChip. We examined the associations between methylation and PFAS levels in maternal serum using robust linear regression models and identified differentially methylated positions (DMPs) and regions (DMRs).
We found four DMPs with a false discovery rate below 0.05 in the discovery cohort. Among the top 20 DMPs ranked by the lowest P-values for perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) exposure, four DMPs showed the same direction of effect and P-value < 0.05 in the replication assay: cg16242615 mapped to ZBTB7A, cg21876869 located in the intergenic region (IGR) of USP2-AS1, cg00173435 mapped to TCP11L2, and cg18901140 located in IGR of NTN1. For DMRs, we found a region associated with PFOA exposure with family-wise error rate < 0.1 located in ZFP57, showing the same direction of effect in the replication cohort. Among the top five DMRs ranked by the lowest P-values that were associated with exposure to PFOS and PFOA, in addition to ZFP57, DMRs in the CYP2E1, SMAD3, SLC17A9, GFPT2, DUSP22, and TCERG1L genes showed the same direction of effect in the replication cohort.
We suggest that prenatal exposure to PFASs may affect DNA methylation status at birth. Longitudinal studies are needed to examine whether methylation changes observed are associated with differential health outcomes.
产前暴露于全氟烷基物质（PFAS）会影响胎儿发育和生命后期。
研究与产前 PFAS 暴露相关的脐带血 DNA 甲基化变化。
我们使用 Illumina HumanMethylation 450 BeadChip 评估了来自北海道研究的 190 对母婴对（发现队列）和来自台湾母婴队列研究的 37 对母婴对（复制队列）的脐带血样本中的 DNA 甲基化。我们使用稳健线性回归模型研究了母体血清中甲基化与 PFAS 水平之间的关联，并确定了差异甲基化位置（DMP）和区域（DMR）。
我们在发现队列中发现了四个具有 False Discovery Rate 低于 0.05 的 DMP。在按全氟辛烷磺酸（PFOS）和全氟辛酸（PFOA）暴露的最低 P 值排名的前 20 个 DMP 中，有四个 DMP 在复制试验中显示出相同的效应方向和 P 值<0.05：映射到 ZBTB7A 的 cg16242615、位于 USP2-AS1 基因间区（IGR）的 cg21876869、映射到 TCP11L2 的 cg00173435 和位于 NTN1 IGR 的 cg18901140。对于 DMR，我们发现了一个与 PFOA 暴露相关的区域，其错误发现率（Family-wise Error Rate）<0.1，位于 ZFP57 中，在复制队列中显示出相同的效应方向。在按与 PFOS 和 PFOA 暴露相关的最低 P 值排名的前五个 DMR 中，除了 ZFP57 之外，CYP2E1、SMAD3、SLC17A9、GFPT2、DUSP22 和 TCERG1L 基因中的 DMR 也在复制队列中显示出相同的效应方向。
我们认为产前 PFAS 暴露可能会影响出生时的 DNA 甲基化状态。需要进行纵向研究，以研究观察到的甲基化变化是否与不同的健康结果相关。
