An epigenome-wide study of cord blood DNA methylations in relation to prenatal perfluoroalkyl substance exposure: The Hokkaido study
An epigenome-wide study of cord blood DNA methylations in relation to prenatal perfluoroalkyl substance exposure: The Hokkaido study
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DOI：
10.1016/j.envint.2018.03.004
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发表时间：
2018-06-01
影响因子：
11.8
通讯作者：
Kishi, Reiko
中科院分区：
文献类型：
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作者：
Miura, Ryu;Araki, Atsuko;Kishi, Reiko
背景资料：产前暴露于全氟烷基化合物（PFASs）对胎儿发育及以后生活的影响目的：探讨产前暴露于PFASs对脐血DNA甲基化的影响。我们评估了北海道研究中札幌队列的190对母子脐带血样本的DNA甲基化使用Illumina HumanMethylation 450 BeadChip，从来自台湾母婴队列研究（Taiwan Maternal and Infant Cohort Study）（复制队列）的37对母子对中进行了比较。我们使用稳健的线性回归模型研究了母体血清中甲基化和PFAS水平之间的相关性，并确定了差异甲基化位置（DMPs）和区域（DMRs）。结果：我们发现了四个DMPs，错误发现率低于0.05。在全氟辛烷磺酸和全氟辛酸接触P值最低的前20种DMPs中，有4种DMPs在重复试验中显示出相同的影响方向，P值< 0.05：cg 16242615定位于ZBTB 7A，cg 21876869定位于USP 2-AS 1的基因间区（IGR），cg 00173435定位于TCP 11 L2，cg 18901140定位于NTN 1的IGR。对于DMR，我们在ZFP 57中发现了一个与PFOA暴露相关的区域，其家族错误率< 0.1，在复制队列中显示了相同的影响方向。在前五名的DMR排名与全氟辛烷磺酸和全氟辛酸，除了ZFP 57，DMR在CYP 2 E1，SMAD 3，SLC 17 A9，GFPT 2，DUSP 22，TCERG 1 L基因的最低P值，显示了相同的方向的效果在replicationcohol.Conclusion：我们认为，产前暴露于全氟辛烷磺酸可能会影响出生时的DNA甲基化状态。需要进行纵向研究，以检查观察到的甲基化变化是否与不同的健康结果相关。
Background: Prenatal exposure to perfluoroalkyl substances (PFASs) influences fetal development and later in life.Objective: To investigate cord blood DNA methylation changes associated with prenatal exposure to PFASs.Methods: 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).Results: 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.Conclusion: 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.