Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Barcelona Institute of Global Health, Barcelona, Spain.
Environ Res. 2024 Oct 15;259:119496. doi: 10.1016/j.envres.2024.119496. Epub 2024 Jun 25.
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.
To investigate associations between PFAS concentrations and miRNA levels in children.
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.
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.
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.
全氟和多氟烷基物质（PFAS）是在环境中持久存在且能在人体内积聚的合成化学物质，导致不良健康影响。microRNAs（miRNAs）是新兴的生物标志物，可以增进对 PFAS 对人类健康影响的机制的理解。然而，人们对 PFAS 暴露与人体内 miRNA 改变之间的关联知之甚少。
研究 PFAS 浓度与儿童 miRNA 水平之间的关联。
利用两个不同队列的数据：美国 Teen-Longitudinal Assessment of Bariatric Surgery（Teen-LABS）队列的 176 名参与者（平均年龄 17.1 岁，75.6%为女性），以及希腊 Rhea 研究的母子队列的 64 名参与者（平均年龄 6.5 岁，39.1%为女性）。从这两项研究中采集了血浆样本，检测了 PFAS 浓度和 miRNA 水平。在调整了协变量后，研究了个体 PFAS 与血浆 miRNA 水平之间的关联。还使用暴露负担评分评估了 PFAS 混合物的累积效应。采用 Ingenuity Pathways Analysis 鉴定与 PFAS 相关的 miRNA 的潜在疾病功能。
在 Teen-LABS 研究中，血浆 PFAS 浓度与 475 个 miRNA 的改变有关，而在 Rhea 研究中则与 5 个 miRNA 的改变有关（FDR p<0.1）。具体而言，血浆 PFAS 浓度与两个队列中 miR-148b-3p 和 miR-29a-3p 的水平降低有关。通路分析表明，与 PFAS 相关的 miRNA 与许多慢性疾病通路有关，包括心血管疾病、炎症和致癌作用。
通过对两个独立队列进行 miRNA 筛选，本研究发现了儿童中与 PFAS 暴露有关的已知和新的 miRNA。通路分析显示，这些 miRNA 参与了几种癌症和炎症相关的通路。需要进一步的研究来增强我们对 PFAS 暴露与疾病风险之间关系的理解，miRNA 作为这些复杂通路中的潜在生物标志物和/或介质正在浮现。
