TY - JOUR
T1 - Exposure to per- and polyfluoroalkyl substances and alterations in plasma microRNA profiles in children
AU - Li, Yijie
AU - Baumert, Brittney O.
AU - Stratakis, Nikos
AU - Goodrich, Jesse A.
AU - Wu, Haotian
AU - Liu, Shelley H.
AU - Wang, Hongxu
AU - Beglarian, Emily
AU - Bartell, Scott M.
AU - Eckel, Sandrah Proctor
AU - Walker, Douglas
AU - Valvi, Damaskini
AU - La Merrill, Michele Andrea
AU - Inge, Thomas H.
AU - Jenkins, Todd
AU - Ryder, Justin R.
AU - Sisley, Stephanie
AU - Kohli, Rohit
AU - Xanthakos, Stavra A.
AU - Vafeiadi, Marina
AU - Margetaki, Aikaterini
AU - Roumeliotaki, Theano
AU - Aung, Max
AU - McConnell, Rob
AU - Baccarelli, Andrea
AU - Conti, David
AU - Chatzi, Lida
N1 - Publisher Copyright:
© 2024
PY - 2024/10/15
Y1 - 2024/10/15
N2 - Background: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that persist in the environment and can accumulate in humans, leading to adverse health effects. MicroRNAs (miRNAs) are emerging biomarkers that can advance the understanding of the mechanisms of PFAS effects on human health. However, little is known about the associations between PFAS exposures and miRNA alterations in humans. Objective: To investigate associations between PFAS concentrations and miRNA levels in children. Methods: Data from two distinct cohorts were utilized: 176 participants (average age 17.1 years; 75.6% female) from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort in the United States, and 64 participants (average age 6.5 years, 39.1% female) from the Rhea study, a mother-child cohort in Greece. PFAS concentrations and miRNA levels were assessed in plasma samples from both studies. Associations between individual PFAS and plasma miRNA levels were examined after adjusting for covariates. Additionally, the cumulative effects of PFAS mixtures were evaluated using an exposure burden score. Ingenuity Pathways Analysis was employed to identify potential disease functions of PFAS-associated miRNAs. Results: Plasma PFAS concentrations were associated with alterations in 475 miRNAs in the Teen-LABs study and 5 miRNAs in the Rhea study (FDR p < 0.1). Specifically, plasma PFAS concentrations were consistently associated with decreased levels of miR-148b-3p and miR-29a-3p in both cohorts. Pathway analysis indicated that PFAS-related miRNAs were linked to numerous chronic disease pathways, including cardiovascular diseases, inflammatory conditions, and carcinogenesis. Conclusion: Through miRNA screenings in two independent cohorts, this study identified both known and novel miRNAs associated with PFAS exposure in children. Pathway analysis revealed the involvement of these miRNAs in several cancer and inflammation-related pathways. Further studies are warranted to enhance our understanding of the relationships between PFAS exposure and disease risks, with miRNA emerging as potential biomarkers and/or mediators in these complex pathways.
AB - Background: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that persist in the environment and can accumulate in humans, leading to adverse health effects. MicroRNAs (miRNAs) are emerging biomarkers that can advance the understanding of the mechanisms of PFAS effects on human health. However, little is known about the associations between PFAS exposures and miRNA alterations in humans. Objective: To investigate associations between PFAS concentrations and miRNA levels in children. Methods: Data from two distinct cohorts were utilized: 176 participants (average age 17.1 years; 75.6% female) from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort in the United States, and 64 participants (average age 6.5 years, 39.1% female) from the Rhea study, a mother-child cohort in Greece. PFAS concentrations and miRNA levels were assessed in plasma samples from both studies. Associations between individual PFAS and plasma miRNA levels were examined after adjusting for covariates. Additionally, the cumulative effects of PFAS mixtures were evaluated using an exposure burden score. Ingenuity Pathways Analysis was employed to identify potential disease functions of PFAS-associated miRNAs. Results: Plasma PFAS concentrations were associated with alterations in 475 miRNAs in the Teen-LABs study and 5 miRNAs in the Rhea study (FDR p < 0.1). Specifically, plasma PFAS concentrations were consistently associated with decreased levels of miR-148b-3p and miR-29a-3p in both cohorts. Pathway analysis indicated that PFAS-related miRNAs were linked to numerous chronic disease pathways, including cardiovascular diseases, inflammatory conditions, and carcinogenesis. Conclusion: Through miRNA screenings in two independent cohorts, this study identified both known and novel miRNAs associated with PFAS exposure in children. Pathway analysis revealed the involvement of these miRNAs in several cancer and inflammation-related pathways. Further studies are warranted to enhance our understanding of the relationships between PFAS exposure and disease risks, with miRNA emerging as potential biomarkers and/or mediators in these complex pathways.
KW - Carcinogenesis
KW - MicroRNA
KW - Per- and polyfluoroalkyl substances
KW - Persistent organic pollutants
KW - Transcriptomics
UR - http://www.scopus.com/inward/record.url?scp=85198018118&partnerID=8YFLogxK
U2 - 10.1016/j.envres.2024.119496
DO - 10.1016/j.envres.2024.119496
M3 - Article
C2 - 38936497
AN - SCOPUS:85198018118
SN - 0013-9351
VL - 259
JO - Environmental Research
JF - Environmental Research
M1 - 119496
ER -