Li Shiwen, Goodrich Jesse A, Chen Jiawen Carmen, Costello Elizabeth, Beglarian Emily, Liao Jiawen, Alderete Tanya L, Valvi Damaskini, Baumert Brittney O, Rock Sarah, Eckel Sandrah P, McConnell Rob, Gilliland Frank D, Chen Zhanghua, Conti David V, Chatzi Lida, Aung Max
Department of Population and Public Health Sciences, University of Southern California Keck School of Medicine, 1845 N. Soto Street, Health Sciences Campus, Los Angeles, CA 90032, USA.
Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Environ Adv. 2024 Oct;17. doi: 10.1016/j.envadv.2024.100585. Epub 2024 Sep 17.
Per-and polyfluoroalkyl substances (PFAS) contamination may disrupt sleep through disrupted metabolic and immune functions. The study aims to investigate the association and potential mechanism between PFAS and sleep.
We included 136 young adults recruited between 2014-2018 and 76 were re-assessed between 2020-2022. Additional 8 participants only had complete data between 2020-2022. Plasma PFAS (PFOS, PFOA, PFHxS, PFHpS, PFPeS, PFNA, PFDA) were measured at both visits using liquid-chromatography high-resolution mass spectrometry. Plasma proteins were measured by Olink Explore 384 Cardiometabolic and Inflammation Panel I. Sleep duration was self-reported at both visits along with follow-up sleep disturbance and sleep-related impairment using validated instruments. We utilized multiple linear regression to explore the association between individual PFAS (in tertile) and these sleep outcomes. PFAS associated with sleep outcomes were subjected to computational toxicology analysis using the Comparative Toxicogenomics Database and Toxicology in the 21st Century database to identify potential genetic links between them. Mediation analysis using proteomic data was then performed to confirm the findings from computational toxicology analysis.
At baseline, one tertile increase in PFDA was associated with 0.39 (95 % CI: 0.05, 0.73) hours of shorter nightly sleep duration, and, at follow-up, PFHxS and PFOA were associated with 0.39 (95 % CI: 0.05, 0.72) and 0.32 (95 % CI: 0.01, 0.63) hours shorter sleep duration, respectively. One tertile increase in PFOS exposure was associated with a 2.99-point increase in sleep disturbance scores (95 % CI: 0.67, 5.31) and a 3.35-point increase in sleep-related impairment scores (95 % CI: 0.51, 6.20). Computational toxicology and mediation analyses identified potential mediating roles for several proteins in the PFAS-sleep associations, including 11-beta-dehydrogenase isozyme 1 (HSD11B1), cathepsin B (CTSB) and several immune system-related proteins.
Future large scale epidemiological and mechanistic studies should confirm our findings and test effect measure modification of the associations by age.
全氟和多氟烷基物质（PFAS）污染可能通过扰乱代谢和免疫功能来干扰睡眠。本研究旨在调查PFAS与睡眠之间的关联及潜在机制。
我们纳入了2014年至2018年间招募的136名年轻成年人，其中76人在2020年至2022年间进行了重新评估。另外8名参与者仅在2020年至2022年间有完整数据。在两次访视时均使用液相色谱高分辨率质谱法测量血浆PFAS（全氟辛烷磺酸、全氟辛酸、全氟己烷磺酸、全氟庚烷磺酸、全氟戊烷磺酸、全氟萘酸、全氟癸二酸）。通过Olink Explore 384心血管代谢和炎症I组检测血浆蛋白。两次访视时均通过经过验证的工具自我报告睡眠时间以及随访期间的睡眠障碍和与睡眠相关的损害情况。我们利用多元线性回归来探索个体PFAS（按三分位数分组）与这些睡眠结果之间的关联。将与睡眠结果相关的PFAS使用比较毒理基因组学数据库和21世纪毒理学数据库进行计算毒理学分析，以确定它们之间潜在的遗传联系。然后使用蛋白质组学数据进行中介分析，以证实计算毒理学分析的结果。
在基线时，全氟癸二酸增加一个三分位数与夜间睡眠时间缩短0.39小时（95%置信区间：0.05，0.73）相关，在随访时，全氟己烷磺酸和全氟辛酸分别与睡眠时间缩短0.39小时（95%置信区间：0.05，0.72）和0.32小时（95%置信区间：0.01，0.63）相关。全氟辛烷磺酸暴露增加一个三分位数与睡眠障碍评分增加2.99分（95%置信区间：0.67，5.31）以及与睡眠相关的损害评分增加3.3分（95%置信区间：0.51，6.20）相关。计算毒理学和中介分析确定了几种蛋白质在PFAS - 睡眠关联中的潜在中介作用，包括11 - β - 脱氢酶同工酶1（HSD11B1）、组织蛋白酶B（CTSB）和几种与免疫系统相关的蛋白质。
未来的大规模流行病学和机制研究应证实我们的发现，并按年龄测试这些关联的效应测量修正情况。
