PMID- 37918745
OWN - NLM
STAT- MEDLINE
DCOM- 20231127
LR  - 20231127
IS  - 1879-1026 (Electronic)
IS  - 0048-9697 (Linking)
VI  - 908
DP  - 2024 Jan 15
TI  - The relationship of organophosphate flame retardants with hyperuricemia and gout 
      via the inflammatory response: An integrated approach.
PG  - 168169
LID - S0048-9697(23)06796-7 [pii]
LID - 10.1016/j.scitotenv.2023.168169 [doi]
AB  - BACKGROUND: Evidence regarding the relationships between organophosphate flame 
      retardants (OPFRs) and hyperuricemia and gout as well as the underlying 
      mechanisms remains scarce, but some evidence indicates that inflammation might 
      play a key role. OBJECTIVES: Using an integrated approach, we aim to elucidate 
      the associations of urinary metabolite OPFRs (m-OPFRs) with hyperuricemia and 
      gout. METHODS: Cross-sectional analyses using data from the National Health and 
      Nutrition Examination Survey were performed to reveal the associations. Adults 
      with complete data on five m-OPFRs with high detection frequencies and outcomes 
      were enrolled. We used multivariate logistic regression, restricted cubic spline 
      (RCS), and Bayesian kernel machine regression (BKMR) methods to account for 
      single, nonlinear, and joint effects. The mediating effect of the inflammatory 
      response was also estimated. Moreover, adverse outcome pathways (AOPs) based on 
      network analysis were further constructed to reveal the underlying mechanism. 
      RESULTS: Multivariate logistic models revealed that bis(2-chloroethyl) phosphate 
      (BCEP) significantly increased risk of hyperuricemia (OR [95 % CI]: 1.165 [1.047, 
      1.296]) in the fully adjusted model. Elevated levels of bis(1-chloro-2-propyl) 
      phosphate were associated with gout (OR [95 % CI]: 1.293 [1.015, 1.647]). No 
      nonlinear relationship was observed in RCS. There was a positive association 
      between mixed m-OPFRs and hyperuricemia risk in BMKR, with 
      bis(1,3-dichloro-2-propyl) phosphate and BCEP being the main contributors 
      (PIP > 0.5). We found that the inflammatory response significantly mediated the 
      association between BCEP and hyperuricemia (P < 0.05). Network topology analysis 
      identified seven genes and six phenotypes related to OPFR exposure and 
      hyperuricemia. The AOP framework suggested that the inflammatory response, 
      especially the activation of the TNF pathway, played a core role in the above 
      relationships. CONCLUSION: Our results first revealed that individual and mixed 
      OPFRs were associated with hyperuricemia, in which the inflammatory response 
      plays an important role. Further longitudinal studies are warranted to 
      consolidate or refute our main findings.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Tan, Yuxuan
AU  - Tan Y
AD  - Department of Epidemiology, School of Medicine, Jinan University, No.601 Huangpu 
      Ave West, Guangzhou 510632, Guangdong, PR China.
FAU - Fu, Yingyin
AU  - Fu Y
AD  - Department of Epidemiology, School of Medicine, Jinan University, No.601 Huangpu 
      Ave West, Guangzhou 510632, Guangdong, PR China.
FAU - Yao, Huojie
AU  - Yao H
AD  - Department of Epidemiology, School of Medicine, Jinan University, No.601 Huangpu 
      Ave West, Guangzhou 510632, Guangdong, PR China.
FAU - Li, Haiying
AU  - Li H
AD  - Department of Epidemiology, School of Medicine, Jinan University, No.601 Huangpu 
      Ave West, Guangzhou 510632, Guangdong, PR China.
FAU - Wu, Xiaomei
AU  - Wu X
AD  - Department of Epidemiology, School of Medicine, Jinan University, No.601 Huangpu 
      Ave West, Guangzhou 510632, Guangdong, PR China.
FAU - Guo, Ziang
AU  - Guo Z
AD  - Department of Epidemiology, School of Medicine, Jinan University, No.601 Huangpu 
      Ave West, Guangzhou 510632, Guangdong, PR China.
FAU - Liang, Xiao
AU  - Liang X
AD  - Department of Epidemiology, School of Medicine, Jinan University, No.601 Huangpu 
      Ave West, Guangzhou 510632, Guangdong, PR China.
FAU - Kuang, Mincong
AU  - Kuang M
AD  - Center for Disease Control and Prevention of Doumen District, Zhuhai 519125, 
      Guangdong, PR China.
FAU - Tan, Lei
AU  - Tan L
AD  - Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, Guangdong, 
      PR China.
FAU - Jing, Chunxia
AU  - Jing C
AD  - Department of Epidemiology, School of Medicine, Jinan University, No.601 Huangpu 
      Ave West, Guangzhou 510632, Guangdong, PR China; Guangdong Key Laboratory of 
      Environmental Pollution and Health, School of Environment, Jinan University, 
      Guangzhou 511443, PR China. Electronic address: jcxphd@gmail.com.
LA  - eng
PT  - Journal Article
DEP - 20231031
PL  - Netherlands
TA  - Sci Total Environ
JT  - The Science of the total environment
JID - 0330500
RN  - 0 (Organophosphates)
RN  - 0 (Flame Retardants)
RN  - 0 (Phosphates)
SB  - IM
MH  - Adult
MH  - Humans
MH  - Organophosphates/metabolism
MH  - *Flame Retardants/analysis
MH  - *Hyperuricemia/chemically induced/epidemiology
MH  - Nutrition Surveys
MH  - Cross-Sectional Studies
MH  - Bayes Theorem
MH  - Phosphates
MH  - *Gout/chemically induced/epidemiology
OTO - NOTNLM
OT  - Adverse outcome pathway
OT  - Co-exposure
OT  - Hyperuricemia
OT  - Inflammation response
OT  - Organophosphate flame retardants
COIS- Declaration of competing interest The authors declare no competing interests.
EDAT- 2023/11/03 00:42
MHDA- 2023/11/27 12:42
CRDT- 2023/11/02 20:19
PHST- 2023/09/07 00:00 [received]
PHST- 2023/10/23 00:00 [revised]
PHST- 2023/10/26 00:00 [accepted]
PHST- 2023/11/27 12:42 [medline]
PHST- 2023/11/03 00:42 [pubmed]
PHST- 2023/11/02 20:19 [entrez]
AID - S0048-9697(23)06796-7 [pii]
AID - 10.1016/j.scitotenv.2023.168169 [doi]
PST - ppublish
SO  - Sci Total Environ. 2024 Jan 15;908:168169. doi: 10.1016/j.scitotenv.2023.168169. 
      Epub 2023 Oct 31.