Abstract：
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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：全氟和多氟烷基物质（PFAS）是在环境中持续存在并可在人体中积累的合成化学物质，导致不利的健康影响。MicroRNAs（miRNA）是新兴的生物标志物，可以促进对PFAS对人类健康影响机制的理解。然而,关于人类PFAS暴露与miRNA改变之间的关联知之甚少。
目的：研究儿童PFAS浓度和miRNA水平之间的关联。
方法：使用来自两个不同队列的数据：176名参与者（平均年龄16.6岁；75.6％为女性）来自美国减肥手术的青少年纵向评估（Teen-LABS）队列，和64名参与者(平均年龄6.5岁，39.1%女性）来自Rhea研究，希腊的一个母子队列。在来自两项研究的血浆样品中评估PFAS浓度和miRNA水平。在调整协变量后检查个体PFAS和血浆miRNA水平之间的关联。此外,使用暴露负担评分评估PFAS混合物的累积效应.采用独创性途径分析来鉴定PFAS相关miRNA的潜在疾病功能。
结果：血浆PFAS浓度与Teen-LABs研究中的476个miRNA和Rhea研究中的13个miRNA的改变相关（FDRp<0.1）。具体来说,在两个队列中,血浆PFAS浓度与miR-148b-3p和miR-29a-3p水平降低一致相关.通路分析表明，PFAS相关的miRNAs与许多慢性疾病通路相关，包括心血管疾病,炎症条件，和致癌作用。
结论：通过两个独立队列中的miRNA筛选，这项研究鉴定了与儿童PFAS暴露相关的已知和新的miRNA。通路分析揭示了这些miRNA参与几种癌症和炎症相关通路。需要进一步的研究来加强我们对PFAS暴露与疾病风险之间关系的理解。miRNA在这些复杂途径中成为潜在的生物标志物和/或介质。
目的：研究儿童PFAS浓度和miRNA水平之间的关联。
方法：使用来自两个不同队列的数据：176名参与者（平均年龄16.6岁；75.6％为女性）来自美国减肥手术的青少年纵向评估（Teen-LABS）队列，和64名参与者(平均年龄6.5岁，39.1%女性）来自Rhea研究，希腊的一个母子队列。在来自两项研究的血浆样品中评估PFAS浓度和miRNA水平。在调整协变量后检查个体PFAS和血浆miRNA水平之间的关联。此外,使用暴露负担评分评估PFAS混合物的累积效应.采用独创性途径分析来鉴定PFAS相关miRNA的潜在疾病功能。
结果：血浆PFAS浓度与Teen-LABs研究中的476个miRNA和Rhea研究中的13个miRNA的改变相关（FDRp<0.1）。具体来说,在两个队列中,血浆PFAS浓度与miR-148b-3p和miR-29a-3p水平降低一致相关.通路分析表明，PFAS相关的miRNAs与许多慢性疾病通路相关，包括心血管疾病,炎症条件，和致癌作用。
结论：通过两个独立队列中的miRNA筛选，这项研究鉴定了与儿童PFAS暴露相关的已知和新的miRNA。通路分析揭示了这些miRNA参与几种癌症和炎症相关通路。需要进一步的研究来加强我们对PFAS暴露与疾病风险之间关系的理解。miRNA在这些复杂途径中成为潜在的生物标志物和/或介质。
