AUTHOR=Chen Li , Chen Lu , Li Xu , Qin Lin , Zhu Yan , Zhang Qianru , Tan Daopeng , He Yuqi , Wang Yu-He 

TITLE=Transcriptomic profiling of hepatic tissues for drug metabolism genes in nonalcoholic fatty liver disease: A study of human and animals

JOURNAL=Frontiers in Endocrinology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.1034494

DOI=10.3389/fendo.2022.1034494

ISSN=1664-2392

ABSTRACT=<sec><title>Background</title><p>Drug metabolism genes are involved in the <italic>in vivo</italic> metabolic processing of drugs. In previous research, we found that a high-fat diet affected the transcript levels of mouse hepatic genes responsible for drug metabolism.</p></sec><sec><title>Aims</title><p>Our research intends to discover the drug metabolism genes that are dysregulated at the transcriptome level in nonalcoholic fatty liver disease (NAFLD).</p></sec><sec><title>Methods</title><p>We analyzed the transcriptome for drug metabolism genes of 35 human liver tissues obtained during laparoscopic cholecystectomy. Additionally, we imported transcriptome data from mice fed a high-fat diet in previous research and two open-access Gene Expression Omnibus (GEO) datasets (GSE63067 and GSE89632). Then, using quantitative real-time polymerase chain reaction (qRT-PCR), we cross-linked the differentially expressed genes (DEGs) in clinical and animal samples and validated the common genes.</p></sec><sec><title>Results</title><p>In this study, we identified 35 DEGs, of which 33 were up-regulated and two were down-regulated. Moreover, we found 71 DEGs (39 up- and 32 down-regulated), 276 DEGs (157 up- and 119 down-regulated), and 158 DEGs (117 up- and 41 down-regulated) in the GSE63067, GSE89632, and high-fat diet mice, respectively. Of the 35 DEGs, nine co-regulated DEGs were found in the Venn diagram (<italic>CYP20A1</italic>, <italic>CYP2U1</italic>, <italic>SLC9A6</italic>, <italic>SLC26A6</italic>, <italic>SLC31A1</italic>, <italic>SLC46A1</italic>, <italic>SLC46A3</italic>, <italic>SULT1B1</italic>, and <italic>UGT2A3).</italic></p></sec><sec><title>Conclusion</title><p>Nine significant drug metabolism genes were identified in NAFLD. Future research should investigate the impacts of these genes on drug dose adjustment in patients with NAFLD.</p></sec><sec><title>Clinical Trial Registration</title><p><uri xlink:href="http://www.chictr.org.cn" xmlns:xlink="http://www.w3.org/1999/xlink">http://www.chictr.org.cn</uri>, identifier ChiCTR2100041714.</p></sec>