{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:10:56Z","timestamp":1791994256298,"version":"4.4.0"},"reference-count":54,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Glucuronidation is a major phase II biotransformation reaction responsible for the inactivation and elimination of endogenous compounds and pharmaceuticals. This process is catalyzed by enzymes belonging to the UDP-glucuronosyltransferase (UGT) family, among which UGT1A1 is the most extensively studied. UGT1A1 plays a critical role in the metabolism of numerous drugs and is essential for bilirubin glucuronidation. Due to this specific function, it has significant clinical relevance, as impaired enzyme activity resulting from genetic polymorphisms or mutations can lead to the accumulation of unconjugated bilirubin in the bloodstream. This study aimed to evaluate the association between the UGT1A1*28 allele and the gene expression and protein levels in human liver tissue, in relation to different liver diseases. Methods: Liver tissues were obtained from patients with various liver pathologies and the control group consisted of tissues showing no pathological symptoms. A total of 143 patients were included in the study. Pyrosequencing was used to analyze PCR products for the UGT1A1*28 polymorphism (variable number of TA repeats in the TATA sequence of the promoter). Results: In both the control and study groups, UGT1A1 gene expression at the mRNA level and protein concentration in liver tissue decreased with the increasing number of UGT1A1*28 alleles. The association between UGT1A1 genotype and mRNA\/protein content was most pronounced in HCV and AIH, and slightly weaker in the ALK and PBC groups. The significant association between UGT1A1*28 allele and bilirubin concentration was observed in control group but not in liver pathology. Conclusions: The UGT1A1*28 polymorphism is associated with reduced hepatic mRNA and protein abundance in patients with liver disease. However, the significance of this observation for the metabolism of the enzyme substrates should be further investigated.<\/jats:p>","DOI":"10.3390\/genes17050589","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T15:02:27Z","timestamp":1779375747000},"page":"589","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Impact of UGT1A1 Genetic Variability on Enzyme Expression in Liver Pathology"],"prefix":"10.3390","volume":"17","author":[{"given":"Sylwia","family":"Szel\u0105g-Pieniek","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Al. Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Kucak","sequence":"additional","affiliation":[{"name":"Independent Pharmacodynamics Laboratory, Pomeranian Medical University, pl. Polskiego Czerwonego Krzy\u017ca 1, 71-244 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8393-9627","authenticated-orcid":false,"given":"Damian","family":"Malinowski","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Monitored Therapy, Pomeranian Medical University, Al. Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6269-4368","authenticated-orcid":false,"given":"Stefan","family":"Oswald","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6191-7168","authenticated-orcid":false,"given":"Marek","family":"Dro\u017adzik","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Al. Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4293-7788","authenticated-orcid":false,"given":"Mateusz","family":"Kurzawski","sequence":"additional","affiliation":[{"name":"Independent Pharmacodynamics Laboratory, Pomeranian Medical University, pl. Polskiego Czerwonego Krzy\u017ca 1, 71-244 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1081\/DMR-120000653","article-title":"The role of hepatic and extrahepatic UDP-glucuronosyltransferases in human drug metabolism","volume":"33","author":"Fisher","year":"2001","journal-title":"Drug Metab. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107","DOI":"10.2174\/1389200003339117","article-title":"Drug-metabolizing enzymes: Mechanisms and functions","volume":"1","author":"Sheweita","year":"2000","journal-title":"Curr. Drug Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"108773","DOI":"10.1016\/j.pharmthera.2024.108773","article-title":"Glucuronidation of orally administered drugs and the value of nanocarriers in strategies for its overcome","volume":"266","author":"Hervieu","year":"2025","journal-title":"Pharmacol. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1080\/03602532.2017.1293682","article-title":"Glucuronidation: Driving factors and their impact on glucuronide disposition","volume":"49","author":"Yang","year":"2017","journal-title":"Drug Metab. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1152\/physrev.00058.2017","article-title":"The UDP-Glycosyltransferase (UGT) superfamily: New members, new functions, and novel paradigms","volume":"99","author":"Meech","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/tpj.2017.5","article-title":"Quantitative profiling of the UGT transcriptome in human drug-metabolizing tissues","volume":"18","author":"Tourancheau","year":"2018","journal-title":"Pharmacogenom. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.biocel.2013.02.019","article-title":"The UDP-glucuronosyltransferases: Their role in drug metabolism and detoxification","volume":"45","author":"Rowland","year":"2013","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1124\/dmd.104.003061","article-title":"Lithocholic acid decreases expression of UGT2B7 in Caco-2 cells: A potential role for a negative farnesoid X receptor response element","volume":"33","author":"Lu","year":"2005","journal-title":"Drug Metab. Dispos."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8749","DOI":"10.1074\/jbc.M610790200","article-title":"Nrf2-Keap1 signaling pathway regulates human UGT1A1 expression in vitro and in transgenic UGT1 mice","volume":"282","author":"Yueh","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1124\/dmd.32.3.340","article-title":"Human PXR variants and their differential effects on the regulation of human UDP-glucuronosyltransferase gene expression","volume":"32","author":"Heydel","year":"2004","journal-title":"Drug Metab. Dispos."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/clpt.2014.126","article-title":"Pharmacogenomics of human uridine diphospho-glucuronosyltransferases and clinical implications","volume":"96","author":"Guillemette","year":"2014","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/03602532.2021.2001493","article-title":"The relationship between UGT1A1 gene and various diseases and prevention strategies","volume":"54","author":"Liu","year":"2022","journal-title":"Drug Metab. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"223","DOI":"10.2217\/bmm.12.4","article-title":"Gilbert syndrome: The UGT1A1*28 promoter polymorphism as a biomarker of multifactorial diseases and drug metabolism","volume":"6","author":"Gil","year":"2012","journal-title":"Biomark. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.jhep.2023.06.004","article-title":"Gilbert\u2019s syndrome revisited","volume":"79","author":"Tiribelli","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_15","first-page":"98503","article-title":"Gilbert\u2019s syndrome: The good, the bad and the ugly","volume":"17","author":"Nuwanshika","year":"2025","journal-title":"World J. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"703","DOI":"10.2217\/14622416.9.6.703","article-title":"Pharmacogenetics of Gilbert\u2019s syndrome","volume":"9","author":"Strassburg","year":"2008","journal-title":"Pharmacogenomics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1253\/circj.CJ-20-0192","article-title":"Serum Bilirubin in the Czech Population\u2014Relationship to the Risk of Myocardial Infarction in Males","volume":"84","author":"Eremiasova","year":"2020","journal-title":"Circ. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6272174","DOI":"10.1155\/2019\/6272174","article-title":"Analysis of the UGT1A1 genotype in hyperbilirubinemia patients: Differences in allele frequency and distribution","volume":"2019","author":"Mi","year":"2019","journal-title":"BioMed Res. Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1124\/mol.104.007161","article-title":"Transcriptional regulation of human UGT1A1 gene expression: Activated glucocorticoid receptor enhances constitutive androstane receptor\/pregnane X receptor-mediated UDP-glucuronosyltransferase 1A1 regulation with glucocorticoid receptor-interacting protein 1","volume":"67","author":"Sugatani","year":"2005","journal-title":"Mol. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"289","DOI":"10.2174\/1389200054633853","article-title":"Xenobiotic nuclear receptor-mediated regulation of UDP-glucuronosyltransferases","volume":"6","author":"Zhou","year":"2005","journal-title":"Curr. Drug Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1080\/03602532.2022.2048846","article-title":"Regulation of human UDP-glycosyltransferase (UGT) genes by miRNAs","volume":"54","author":"Hu","year":"2022","journal-title":"Drug Metab. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1002\/cpt.3529","article-title":"Inhibition of OATP1B1\/3 rather than UGT1A1 may be the major cause of the bilirubin elevation after atazanavir administration","volume":"118","author":"Dong","year":"2024","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3122","DOI":"10.1200\/JCO.2002.08.177","article-title":"Modulation of irinotecan metabolism by ketoconazole","volume":"20","author":"Kehrer","year":"2002","journal-title":"J. Clin. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1097\/01.fpc.0000182784.77630.48","article-title":"Study of the genetic determinants of UGT1A1 inducibility by phenobarbital in cultured human hepatocytes","volume":"16","author":"Komoroski","year":"2006","journal-title":"Pharmacogenet. Genom."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1002\/bmc.1345","article-title":"Irinotecan and its active metabolite, SN-38: Review of bioanalytical methods and recent update from clinical pharmacology perspectives","volume":"24","author":"Ramesh","year":"2010","journal-title":"Biomed. Chromatogr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e479","DOI":"10.1111\/ajco.13028","article-title":"UGT1A1*6 and UGT1A1*28 polymorphisms are correlated with irinotecan-induced toxicity: A meta-analysis","volume":"14","author":"Yang","year":"2018","journal-title":"Asia Pac. J. Clin. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.phrs.2016.01.002","article-title":"UGT genotyping in belinostat dosing","volume":"105","author":"Goey","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1080\/00498254.2016.1183061","article-title":"In vitro characterization of belinostat glucuronidation: Demonstration of both UGT1A1 and UGT2B7 as the main contributing isozymes","volume":"47","author":"Dong","year":"2017","journal-title":"Xenobiotica"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1002\/hep.20770","article-title":"UGT1A1 polymorphisms are important determinants of dietary carcinogen detoxification in the liver","volume":"42","author":"Girard","year":"2005","journal-title":"Hepatology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1097\/FPC.0b013e3280121fe9","article-title":"UGT1A1*28 genotype affects the in vitro glucuronidation of thyroxine in human livers","volume":"17","author":"Innocenti","year":"2007","journal-title":"Pharmacogenet. Genom."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1007\/s11596-017-1797-6","article-title":"Correlation between UGT1A1 polymorphism and neonatal hyperbilirubinemia of neonates in Wuhan","volume":"37","author":"Liu","year":"2017","journal-title":"Curr. Med. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s00228-016-2137-7","article-title":"Hepatic expression of transcription factors affecting developmental regulation of UGT1A1 in the Han Chinese population","volume":"73","author":"Nie","year":"2017","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Taylor, M.J., Collins, J.M., Montalvo, A.D., and Wang, D. (2025). Association between UGT1A1 mRNA expression and cis-acting genetic variants and trans-acting transcriptional regulators in human liver samples. Genes, 16.","DOI":"10.3390\/genes16080971"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Dro\u017adzik, M., Lapczuk-Romanska, J., Wenzel, C., Szelag-Pieniek, S., Post, M., Skalski, \u0141., Kurzawski, M., and Oswald, S. (2021). Gene expression and protein abundance of hepatic drug metabolizing enzymes in liver pathology. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13091334"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Dro\u017adzik, M., Lapczuk-Romanska, J., Wenzel, C., Skalski, L., Szel\u0105g-Pieniek, S., Post, M., Parus, A., Syczewska, M., Kurzawski, M., and Oswald, S. (2023). Protein abundance of drug metabolizing enzymes in human hepatitis C livers. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054543"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1007\/s43440-021-00290-8","article-title":"Hepatic drug-metabolizing enzymes and drug transporters in Wilson\u2019s disease patients with liver failure","volume":"73","author":"Oswald","year":"2021","journal-title":"Pharmacol. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1002\/jcla.21820","article-title":"Development of pyrosequencing method for detection of UGT1A1 polymorphisms in Thai colorectal cancers","volume":"30","author":"Sukasem","year":"2016","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1002\/cpt.967","article-title":"Protein abundance of clinically relevant drug-metabolizing enzymes in the human liver and intestine: A comparative analysis in paired tissue specimens","volume":"104","author":"Busch","year":"2018","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1111\/j.1365-2125.2007.02923.x","article-title":"Limited influence of UGT1A1*28 and no effect of UGT2B7*2 polymorphisms on UGT1A1 or UGT2B7 activities and protein expression in human liver microsomes","volume":"64","author":"Peterkin","year":"2007","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_40","first-page":"020501","article-title":"Bilirubin\u2014New insights into an old molecule","volume":"35","author":"Dodig","year":"2025","journal-title":"Biochem. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5558","DOI":"10.1093\/hmg\/ddu268","article-title":"Genetic factors affecting gene transcription and catalytic activity of UDP-glucuronosyltransferases in human liver","volume":"23","author":"Liu","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1559325817723731","DOI":"10.1177\/1559325817723731","article-title":"Effect of UDP-glucuronosyltransferase (UGT) 1A polymorphism (rs8330 and rs10929303) on glucuronidation status of acetaminophen","volume":"15","author":"Mehboob","year":"2017","journal-title":"Dose Response"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1097\/FTD.0000000000000154","article-title":"Functional study of haplotypes in UGT1A1 promoter to find a novel genetic variant leading to reduced gene expression","volume":"37","author":"Shin","year":"2015","journal-title":"Ther. Drug Monit."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1111\/apt.16489","article-title":"Review article: Time to revisit Child-Pugh score as the basis for predicting drug clearance in hepatic impairment","volume":"54","author":"Darwich","year":"2021","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e2877","DOI":"10.1097\/MD.0000000000002877","article-title":"Child-Pugh versus MELD score for the assessment of prognosis in liver cirrhosis: A systematic review and meta-analysis of observational studies","volume":"95","author":"Peng","year":"2016","journal-title":"Medicine"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1053\/jhep.2001.24101","article-title":"Characterization of autoantibodies against uridine-diphosphate glucuronosyltransferase in patients with inflammatory liver diseases","volume":"33","author":"Bachrich","year":"2001","journal-title":"Hepatology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"45","DOI":"10.2478\/jomb-2018-0015","article-title":"Significance of UGT1A1*28 genotype in patients with advanced liver injury caused by chronic hepatitis C","volume":"38","author":"Jordovic","year":"2019","journal-title":"J. Med. Biochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/S1665-2681(19)31511-X","article-title":"No association of promoter variations of HMOX1 and UGT1A1 genes with liver injury in chronic hepatitis C","volume":"10","author":"Hrabal","year":"2011","journal-title":"Ann. Hepatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e41192","DOI":"10.1097\/MD.0000000000041192","article-title":"Primary sclerosing cholangitis with PLKR and UGT1A1 mutation manifested as recurrent bile duct stones: A case report","volume":"104","author":"Zhou","year":"2025","journal-title":"Medicine"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Lenoir, C., Rollason, V., Desmeules, J.A., and Samer, C.F. (2021). Influence of inflammation on cytochromes P450 activity in adults: A systematic review of the literature. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.733935"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Daujat-Chavanieu, M., and Gerbal-Chaloin, S. (2020). Regulation of CAR and PXR expression in health and disease. Cells, 9.","DOI":"10.3390\/cells9112395"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.phrs.2017.05.001","article-title":"UDP-glucuronosyltransferases (UGTs) and their related metabolic cross-talk with internal homeostasis: A systematic review of UGT isoforms for precision medicine","volume":"121","author":"Yang","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Yi, F., Tao, S., and Wu, H. (2025). Bilirubin metabolism in relation to cancer. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1570288"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1007\/s43440-021-00337-w","article-title":"The reference liver\u2014CYP450 and UGT enzymes in healthy donor and metastatic livers: The impact of genotype","volume":"74","author":"Kurzawski","year":"2022","journal-title":"Pharmacol. Rep."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/5\/589\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T15:12:52Z","timestamp":1779376372000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/5\/589"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,21]]},"references-count":54,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["genes17050589"],"URL":"https:\/\/doi.org\/10.3390\/genes17050589","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,21]]}}}