Department of Epidemiology, Brown University School of Public Health, Providence, Rhode Island, USA.
Department of Biostatistics, Brown University School of Public Health, Providence, Rhode Island, USA.
Environ Health Perspect. 2022 Mar;130(3):37005. doi: 10.1289/EHP10118. Epub 2022 Mar 10.
DNA methylation alterations may underlie associations between gestational perfluoroalkyl substances (PFAS) exposure and later-life health outcomes. To the best of our knowledge, no longitudinal studies have examined the associations between gestational PFAS and DNA methylation.
We examined associations of gestational PFAS exposure with longitudinal DNA methylation measures at birth and in adolescence using the Health Outcomes and Measures of the Environment (HOME) Study (2003-2006; Cincinnati, Ohio).
We quantified serum concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), and perfluorohexane sulfonate (PFHxS) in mothers during pregnancy. We measured DNA methylation in cord blood () and peripheral leukocytes at 12 years of age () using the Illumina HumanMethylation EPIC BeadChip. We analyzed associations between PFAS concentrations and repeated DNA methylation measures using linear regression with generalized estimating equations. We included interaction terms between children's age and gestational PFAS. We performed Gene Ontology enrichment analysis to identify molecular pathways. We used Project Viva (1999-2002; Boston, Massachusetts) to replicate significant associations.
After adjusting for covariates, 435 cytosine-guanine dinucleotide (CpG) sites were associated with PFAS (false discovery rate, ). Specifically, we identified 2 CpGs for PFOS, 12 for PFOA, 8 for PFHxS, and 413 for PFNA; none overlapped. Among these, 2 CpGs for PFOA and 4 for PFNA were replicated in Project Viva. Some of the PFAS-associated CpG sites annotated to gene regions related to cancers, cognitive health, cardiovascular disease, and kidney function. We found little evidence that the associations between PFAS and DNA methylation differed by children's age.
In these longitudinal data, PFAS biomarkers were associated with differences in several CpGs at birth and at 12 years of age in or near genes linked to some PFAS-associated health outcomes. Future studies should examine whether DNA methylation mediates associations between gestational PFAS exposure and health. https://doi.org/10.1289/EHP10118.
DNA 甲基化的改变可能是妊娠期全氟烷基物质（PFAS）暴露与晚年健康结果之间关联的基础。据我们所知，目前还没有纵向研究检验妊娠期 PFAS 与 DNA 甲基化之间的关系。
我们使用环境健康展望研究（HOME）（2003-2006 年；俄亥俄州辛辛那提），检测了妊娠期 PFAS 暴露与出生时和青少年时期纵向 DNA 甲基化测量值之间的关联。
我们在妊娠期间定量检测了母亲血清中全氟辛烷磺酸（PFOS）、全氟辛酸（PFOA）、全氟壬酸（PFNA）和全氟己烷磺酸（PFHxS）的浓度。我们使用 Illumina HumanMethylation EPIC BeadChip 分别在脐带血（）和 12 岁时的外周血白细胞（）中测量了 DNA 甲基化。我们使用广义估计方程的线性回归分析了 PFAS 浓度与重复 DNA 甲基化测量值之间的关系。我们还包括了儿童年龄与妊娠期 PFAS 之间的交互项。我们进行了基因本体论富集分析，以确定分子途径。我们使用了项目生命力（1999-2002 年；马萨诸塞州波士顿）来复制有显著关联的结果。
在调整了协变量后，有 435 个胞嘧啶-鸟嘌呤二核苷酸（CpG）位点与 PFAS 相关（错误发现率，）。具体来说，我们鉴定出 2 个与 PFOS 相关的 CpG 位点，12 个与 PFOA 相关的 CpG 位点，8 个与 PFHxS 相关的 CpG 位点，以及 413 个与 PFNA 相关的 CpG 位点；这些 CpG 位点没有重叠。其中，PFOA 与 2 个 CpG 位点和 PFNA 与 4 个 CpG 位点在项目生命力中得到了复制。一些与 PFAS 相关的 CpG 位点注释到与癌症、认知健康、心血管疾病和肾功能相关的基因区域。我们发现，PFAS 与 DNA 甲基化之间的关联在儿童年龄上几乎没有差异。
在这些纵向数据中，PFAS 生物标志物与出生时和 12 岁时的几个 CpG 位点相关，这些 CpG 位点位于与某些 PFAS 相关健康结果相关的基因区域附近或之内。未来的研究应该检测 DNA 甲基化是否介导了妊娠期 PFAS 暴露与健康之间的关联。https://doi.org/10.1289/EHP10118.
