PMID- 38163401
OWN - NLM
STAT- MEDLINE
DCOM- 20240125
LR  - 20240202
IS  - 1873-6750 (Electronic)
IS  - 0160-4120 (Linking)
VI  - 183
DP  - 2024 Jan
TI  - Overall and individual associations between per- and polyfluoroalkyl substances 
      and liver function indices and the metabolic mechanism.
PG  - 108405
LID - S0160-4120(23)00678-5 [pii]
LID - 10.1016/j.envint.2023.108405 [doi]
AB  - Per- and polyfluoroalkyl substances (PFAS) can disrupt liver homeostasis. Studies 
      have shown that a single exposure to PFAS may provoke abnormal liver function; 
      however, few studies have investigated the overall effect of PFAS mixtures. We 
      aimed to investigate associations between exposure to PFAS mixtures and liver 
      function indices and explore the relevant mechanisms. This study included 278 
      adult males from Guangzhou, China. Serum metabolite profiles were analyzed using 
      untargeted metabolomics. We applied weighted quantile sum (WQS) regression as 
      well as Bayesian kernel machine regression (BKMR) to analyze the association of 
      nine PFAS mixtures with 14 liver function indices. PFAS mixtures were positively 
      associated with apolipoprotein B (APOB) and gamma-glutamyltransferase (GGT) and 
      negatively associated with direct bilirubin (DBIL) and total bilirubin (TBIL) in 
      both the WQS and BKMR analyses. In addition, Spearman's correlation test showed 
      individual PFAS correlated with APOB, GGT, TBIL, and DBIL, while there's little 
      correlation between individual PFAS and other liver function indices. In linear 
      regression analysis, PFHxS, PFOS, PFHpS, PFNA, PFDA, and PFUdA were associated 
      with APOB; PFOA, PFDA, PFOS, PFNA, and PFUdA were associated with GGT. 
      Subsequently, a metabolome-wide association study and mediation analysis were 
      combined to explore metabolites that mediate these associations. The mechanisms 
      linking PFAS to APOB and GGT are mainly related with amino acid and 
      glycerophospholipid metabolism. High-dimensional mediation analysis showed that 
      glycerophospholipids are the main markers of the association between PFAS and 
      APOB, and that (R)-dihydromaleimide, Ile Leu, (R)-(+)-2-pyrrolidone-5-carboxylic 
      acid, and L-glutamate are the main markers of the association between PFAS and 
      GGT. In summary, overall associations between PFAS and specific indices of liver 
      function were found using two statistical methods; the metabolic pathways and 
      markers identified here may serve to prompt more detailed study in animal-based 
      systems, as well as a similar detailed analysis in other populations.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Chen, Yiran
AU  - Chen Y
AD  - Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China; 
      School of Public Health, Southern Medical University, Guangzhou 510515, China.
FAU - Wu, Yan
AU  - Wu Y
AD  - Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China.
FAU - Lv, Jiayun
AU  - Lv J
AD  - Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China.
FAU - Zhou, Si
AU  - Zhou S
AD  - Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China.
FAU - Lin, Shaobin
AU  - Lin S
AD  - School of Public Health, Southern Medical University, Guangzhou 510515, China.
FAU - Huang, Suli
AU  - Huang S
AD  - School of Public Health, Shenzhen University Medical School, Shenzhen University, 
      Shenzhen 518055, China.
FAU - Zheng, Linjie
AU  - Zheng L
AD  - School of Public Health, Southern Medical University, Guangzhou 510515, China.
FAU - Deng, Guanhua
AU  - Deng G
AD  - Key Laboratory of Occupational Environment and Health, Guangzhou Twelfth People's 
      Hospital, Guangzhou 510620, China.
FAU - Feng, Yuchao
AU  - Feng Y
AD  - Key Laboratory of Occupational Environment and Health, Guangzhou Twelfth People's 
      Hospital, Guangzhou 510620, China.
FAU - Zhang, Guoxia
AU  - Zhang G
AD  - School of Public Health, Southern Medical University, Guangzhou 510515, China.
FAU - Feng, Wenru
AU  - Feng W
AD  - Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China. 
      Electronic address: gzcdchwk@163.com.
LA  - eng
PT  - Journal Article
DEP - 20231222
PL  - Netherlands
TA  - Environ Int
JT  - Environment international
JID - 7807270
RN  - 0 (Apolipoproteins B)
RN  - RFM9X3LJ49 (Bilirubin)
RN  - 0 (Fluorocarbons)
RN  - 0 (Environmental Pollutants)
RN  - 0 (Alkanesulfonic Acids)
SB  - IM
MH  - Animals
MH  - Male
MH  - Bayes Theorem
MH  - Apolipoproteins B
MH  - Bilirubin
MH  - Liver
MH  - *Fluorocarbons
MH  - *Environmental Pollutants
MH  - *Alkanesulfonic Acids
OTO - NOTNLM
OT  - Association
OT  - Liver function
OT  - Mechanism
OT  - Metabolomics
OT  - PFAS
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2024/01/02 11:41
MHDA- 2024/01/25 06:43
CRDT- 2024/01/01 18:00
PHST- 2023/05/01 00:00 [received]
PHST- 2023/11/06 00:00 [revised]
PHST- 2023/12/20 00:00 [accepted]
PHST- 2024/01/25 06:43 [medline]
PHST- 2024/01/02 11:41 [pubmed]
PHST- 2024/01/01 18:00 [entrez]
AID - S0160-4120(23)00678-5 [pii]
AID - 10.1016/j.envint.2023.108405 [doi]
PST - ppublish
SO  - Environ Int. 2024 Jan;183:108405. doi: 10.1016/j.envint.2023.108405. Epub 2023 
      Dec 22.