Perfluorooctanoic acid (PFOA) or perfluorooctane sulfonate (PFOS) and DNA methylation in newborn dried blood spots in the upstate KIDS cohort

Authors: ROBINSON, SONIA - NATIONAL INSTITUTES OF HEALTH (NIH); ZENG, XUEHUO - GLOTECH, INC.; GUAN, WEIHUA - UNIVERSITY OF MINNESOTA; SUNDARAM, RAJESHWARI - NATIONAL INSTITUTES OF HEALTH (NIH); MENDOLA, PAULINE - UNIVERSITY AT BUFFALO; PUTKICK, DIANE - NATIONAL INSTITUTES OF HEALTH (NIH); WATERLAND, ROBERT - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC); GANASEKARA, CHATHURA - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC); KANNAN, KURUNTHACHALAM - NEW YORK UNIVERSITY SCHOOL OF MEDICINE; GAO, CHONGJING - NEW YORK UNIVERSITY SCHOOL OF MEDICINE; BELL, ERINM - ALBANY STATE UNIVERSITY; YEUNG, EDWINA - NATIONAL INSTITUTES OF HEALTH (NIH)

Submitted to: Environmental Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/22/2020
Publication Date: 3/1/2021
Citation: Robinson, S.L., Zeng, X., Guan, W., Sundaram, R., Mendola, P., Putkick, D.L., Waterland, R.A., Ganasekara, C., Kannan, K., Gao, C., Bell, E., Yeung, E.H. 2021. Perfluorooctanoic acid (PFOA) or perfluorooctane sulfonate (PFOS) and DNA methylation in newborn dried blood spots in the upstate KIDS cohort. Environmental Research. 194:110668. https://doi.org/10.1016/j.envres.2020.110668.
DOI: https://doi.org/10.1016/j.envres.2020.110668

Interpretive Summary: Epigenetics is a system for molecular marking of DNA – it tells the different cells in the body which genes to turn on or off in that cell type. A key epigenetic mechanism is methylation of cytosine nucleotides in DNA. Once established during development, DNA methylation can stably silence gene expression. There is growing interest in the idea that exposure to environmental contaminants during critical periods of development can have long-term deleterious consequences by affecting the establishment of DNA methylation. To test this, in this study we focused on two persistent organic pollutants, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), which can be found in everyday household products. We tested associations between PFOA and PFOS exposure and DNA methylation in cord blood of 597 newborns in the Upstate Kids cohort study. We found limited evidence of an association between high concentrations of PFOA and PFOS and DNA methylation in newborns, suggesting that future studies examine populations with higher median levels of exposure to these environmental contaminants.

Technical Abstract: Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are persistent organic pollutants which may alter prenatal development, potentially through epigenetic modifications. Prior studies examining PFOS/PFOA and DNA methylation have relatively few subjects (n < 200) and inconsistent results. We examined relations of PFOA/PFOS with DNA methylation among 597 neonates in the Upstate KIDS cohort study. PFOA/PFOS were quantified in newborn dried blood spots (DBS) using high-performance liquid chromatography/tandem mass spectrometry. DNA methylation was measured using the Infinium MethylationEPIC BeadChip with DNA extracted from DBS. Robust linear regression was used to examine the associations of PFOA/PFOS with DNA methylation at individual CpG sites. Covariates included sample plate, estimated cell type, epigenetically derived ancestry, infant sex and plurality, indicators of maternal socioeconomic status, and prior pregnancy loss. In supplemental analysis, we restricted the analysis to 2242 CpG sites previously identified as Correlated Regions of Systemic Interindividual Variation (CoRSIVs) which include metastable epialleles. At FDR<0.05, PFOA concentration >90th percentile was related to DNA methylation at cg15557840, near SCRT2, SRXN1; PFOS>90th percentile was related to 2 CpG sites in a sex-specific manner (cg19039925 in GVIN1 in boys and cg05754408 in ZNF26 in girls). When analysis was restricted to CoRSIVs, log-scaled, continuous PFOS concentration was related to DNA methylation at cg03278866 within PTBP1. In conclusion, there was limited evidence of an association between high concentrations of PFOA/PFOS and DNA methylation in newborn DBS in the Upstate KIDS cohort. These findings merit replication in populations with a higher median concentration of PFOA/PFOS.