Liu Yun, Gairola Richa, Kuiper Jordan R, Papandonatos George D, Kelsey Karl T, Langevin Scott M, Buckley Jessie P, Chen Aimin, Lanphear Bruce P, Cecil Kim M, Yolton Kimberly, Braun Joseph M
Department of Epidemiology, Brown University School of Public Health, Providence, RI, 02903, USA.
Department of Environmental and Occupational Health, George Washington University Milken Institute School of Public Health, Washington, D.C., 20037, USA.
Environ Sci Technol Lett. 2023 Oct 10;10(10):824-830. doi: 10.1021/acs.estlett.3c00410. Epub 2023 Sep 1.
Per- and polyfluoroalkyl substance (PFAS) exposure has been linked to DNA methylation changes in neonates and adults. We previously reported that prenatal PFAS exposure may have a durable impact on DNA methylation from birth to adolescence. However, few studies have examined the association of postnatal PFAS exposure with alterations in DNA methylation. We examined the associations of lifetime postnatal PFAS mixture exposure with leukocyte DNA methylation in 154 adolescents from the HOME Study (2003-2006; Cincinnati, Ohio). Lifetime postnatal PFAS mixture exposure was estimated using latent profile analysis of four PFAS concentrations measured at birth, and ages 3, 8, and 12 years. We measured DNA methylation in peripheral leukocytes at 12 years using the Illumina HumanMethylation EPIC BeadChip. We estimated covariate-adjusted associations between postnatal PFAS mixture concentrations and DNA methylation measures using linear regression, and used KEGG enrichment analysis to identify molecular pathways. Four significant differentially methylated positions were observed in the higher vs. lower PFAS profile (FDR p-value <0.05). These PFAS-associated CpG sites annotated to gene regions related to various cancers, cognition, and cardiometabolic health. We identified 17 pathways (FDR p-value <0.05), which indicates possible mechanism linking PFAS exposure to several health effects.
全氟和多氟烷基物质（PFAS）暴露与新生儿及成年人的DNA甲基化变化有关。我们之前报道过，产前PFAS暴露可能对从出生到青春期的DNA甲基化产生持久影响。然而，很少有研究探讨产后PFAS暴露与DNA甲基化改变之间的关联。我们在来自HOME研究（2003 - 2006年；俄亥俄州辛辛那提）的154名青少年中，研究了终生产后PFAS混合物暴露与白细胞DNA甲基化之间的关联。终生产后PFAS混合物暴露是通过对出生时以及3岁、8岁和12岁时测量的四种PFAS浓度进行潜在剖面分析来估计的。我们在12岁时使用Illumina HumanMethylation EPIC BeadChip测量外周血白细胞中的DNA甲基化。我们使用线性回归估计产后PFAS混合物浓度与DNA甲基化测量值之间经协变量调整后的关联，并使用KEGG富集分析来确定分子途径。在较高PFAS剖面与较低PFAS剖面中观察到四个显著的差异甲基化位点（FDR p值<0.05）。这些与PFAS相关的CpG位点注释到与各种癌症、认知和心脏代谢健康相关的基因区域。我们确定了17条途径（FDR p值<0.05），这表明了将PFAS暴露与多种健康影响联系起来的可能机制。
