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Potential genomic biomarkers of obesity and its comorbidities for phthalates and bisphenol A mixture: In silico toxicogenomic approach

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2022
Potential_genomic_biomarkers_pub_2022.pdf (797.3Kb)
Authors
Baralić, Katarina
Živančević, Katarina
Božić, Dragica
Jennen, Danyel
Buha-Đorđević, Aleksandra
Antonijević-Miljaković, Evica
Đukić-Ćosić, Danijela
Article (Published version)
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Abstract
This in silico toxicogenomic study aims to explore the relationship between phthalates and bisphenol A (BPA) co-exposure and obesity, as well as its comorbid conditions, in order to construct a possible set of genomic biomarkers. The Comparative Toxicogenomics Database (CTD; http://ctd.mdibl.org) was used as the main data mining tool, along with GeneMania (https://genemania.org), ToppGene Suite (https://toppgene.cchmc.org) and DisGeNET (http://www. disgenet.org). Among the phthalates, bis(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) were chosen as the most frequently curated phthalates in CTD, which also share similar mechanisms of toxicity. DEHP, DBP and BPA interacted with 84, 90 and 194 obesity-related genes/proteins, involved in 67, 65 and 116 pathways, respectively. Among these, 53 genes/proteins and 42 pathways were common to all three substances. 31 genes/proteins had matching interactions for all three investigated substances, while more than half of these genes/p...roteins (56.49%) were in co-expression. 7 of the common genes/proteins (6 relevant to humans: CCL2, IL6, LPL, PPARG, SERPINE1, and TNF) were identified in all the investigated obesity comorbidities, while PPARG and LPL were most closely linked to obesity. These genes/proteins could serve as a target for further in vitro and in vivo studies of molecular mechanisms of DEHP, DBP and BPA mixture obesogenic properties. Analysis reported here should be applicable to any mixture of environmental chemicals and any disease present in CTD.

Keywords:
Endocrine disruptors / Bioinformatics / Data mining / Toxicology
Source:
Biocell, 2022, 46, 2, 519-533
Publisher:
  • Tech Science Press
Funding / projects:
  • Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200161 (University of Belgrade, Faculty of Pharmacy) (RS-200161)

DOI: 10.32604/biocell.2022.018271

ISSN: 0327-9545

WoS: 000710185900008

Scopus: 2-s2.0-85122861485
[ Google Scholar ]
5
1
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/4026
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - JOUR
AU  - Baralić, Katarina
AU  - Živančević, Katarina
AU  - Božić, Dragica
AU  - Jennen, Danyel
AU  - Buha-Đorđević, Aleksandra
AU  - Antonijević-Miljaković, Evica
AU  - Đukić-Ćosić, Danijela
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4026
AB  - This in silico toxicogenomic study aims to explore the relationship between phthalates and bisphenol A (BPA) co-exposure and obesity, as well as its comorbid conditions, in order to construct a possible set of genomic biomarkers. The Comparative Toxicogenomics Database (CTD; http://ctd.mdibl.org) was used as the main data mining tool, along with GeneMania (https://genemania.org), ToppGene Suite (https://toppgene.cchmc.org) and DisGeNET (http://www. disgenet.org). Among the phthalates, bis(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) were chosen as the most frequently curated phthalates in CTD, which also share similar mechanisms of toxicity. DEHP, DBP and BPA interacted with 84, 90 and 194 obesity-related genes/proteins, involved in 67, 65 and 116 pathways, respectively. Among these, 53 genes/proteins and 42 pathways were common to all three substances. 31 genes/proteins had matching interactions for all three investigated substances, while more than half of these genes/proteins (56.49%) were in co-expression. 7 of the common genes/proteins (6 relevant to humans: CCL2, IL6, LPL, PPARG, SERPINE1, and TNF) were identified in all the investigated obesity comorbidities, while PPARG and LPL were most closely linked to obesity. These genes/proteins could serve as a target for further in vitro and in vivo studies of molecular mechanisms of DEHP, DBP and BPA mixture obesogenic properties. Analysis reported here should be applicable to any mixture of environmental chemicals and any disease present in CTD.
PB  - Tech Science Press
T2  - Biocell
T1  - Potential genomic biomarkers of obesity and its comorbidities for phthalates and bisphenol A mixture: In silico toxicogenomic approach
VL  - 46
IS  - 2
SP  - 519
EP  - 533
DO  - 10.32604/biocell.2022.018271
ER  - 
@article{
author = "Baralić, Katarina and Živančević, Katarina and Božić, Dragica and Jennen, Danyel and Buha-Đorđević, Aleksandra and Antonijević-Miljaković, Evica and Đukić-Ćosić, Danijela",
year = "2022",
abstract = "This in silico toxicogenomic study aims to explore the relationship between phthalates and bisphenol A (BPA) co-exposure and obesity, as well as its comorbid conditions, in order to construct a possible set of genomic biomarkers. The Comparative Toxicogenomics Database (CTD; http://ctd.mdibl.org) was used as the main data mining tool, along with GeneMania (https://genemania.org), ToppGene Suite (https://toppgene.cchmc.org) and DisGeNET (http://www. disgenet.org). Among the phthalates, bis(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) were chosen as the most frequently curated phthalates in CTD, which also share similar mechanisms of toxicity. DEHP, DBP and BPA interacted with 84, 90 and 194 obesity-related genes/proteins, involved in 67, 65 and 116 pathways, respectively. Among these, 53 genes/proteins and 42 pathways were common to all three substances. 31 genes/proteins had matching interactions for all three investigated substances, while more than half of these genes/proteins (56.49%) were in co-expression. 7 of the common genes/proteins (6 relevant to humans: CCL2, IL6, LPL, PPARG, SERPINE1, and TNF) were identified in all the investigated obesity comorbidities, while PPARG and LPL were most closely linked to obesity. These genes/proteins could serve as a target for further in vitro and in vivo studies of molecular mechanisms of DEHP, DBP and BPA mixture obesogenic properties. Analysis reported here should be applicable to any mixture of environmental chemicals and any disease present in CTD.",
publisher = "Tech Science Press",
journal = "Biocell",
title = "Potential genomic biomarkers of obesity and its comorbidities for phthalates and bisphenol A mixture: In silico toxicogenomic approach",
volume = "46",
number = "2",
pages = "519-533",
doi = "10.32604/biocell.2022.018271"
}
Baralić, K., Živančević, K., Božić, D., Jennen, D., Buha-Đorđević, A., Antonijević-Miljaković, E.,& Đukić-Ćosić, D.. (2022). Potential genomic biomarkers of obesity and its comorbidities for phthalates and bisphenol A mixture: In silico toxicogenomic approach. in Biocell
Tech Science Press., 46(2), 519-533.
https://doi.org/10.32604/biocell.2022.018271
Baralić K, Živančević K, Božić D, Jennen D, Buha-Đorđević A, Antonijević-Miljaković E, Đukić-Ćosić D. Potential genomic biomarkers of obesity and its comorbidities for phthalates and bisphenol A mixture: In silico toxicogenomic approach. in Biocell. 2022;46(2):519-533.
doi:10.32604/biocell.2022.018271 .
Baralić, Katarina, Živančević, Katarina, Božić, Dragica, Jennen, Danyel, Buha-Đorđević, Aleksandra, Antonijević-Miljaković, Evica, Đukić-Ćosić, Danijela, "Potential genomic biomarkers of obesity and its comorbidities for phthalates and bisphenol A mixture: In silico toxicogenomic approach" in Biocell, 46, no. 2 (2022):519-533,
https://doi.org/10.32604/biocell.2022.018271 . .

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