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

作　　者：KATARINA BARALIĆ KATARINAŽIVANČEVIĆ DRAGICA BOŽIĆ DANYEL JENNEN ALEKSANDRA BUHA DJORDJEVIC EVICA ANTONIJEVIĆMILJAKOVIĆ 

机构地区：[1]DANIJELAĐUKIĆ-ĆOSIĆ11 Department of Toxicology“Akademik Danilo Soldatović”,University of Belgrade-Faculty of Pharmacy,Belgrade,11000,Serbia [2]Department of Toxicogenomics,GROW School for Oncology and Developmental Biology,Maastricht University,Maastricht,6221,The Netherlands

出　　处：《BIOCELL》2022年第2期519-533,共15页生物细胞（英文）

基　　金：supported by TheMinistry of Education,Science and Technological Development of the Republic of Serbia[Contact Number 451-03-9/2021-14/200161].

摘　　要：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.

关 键 词：Endocrine disruptors Data mining BIOINFORMATICS TOXICOLOGY 

分 类 号：R11[医药卫生—公共卫生与预防医学]