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Olanzapine treatment sometimes produces transient liver biochemistry abnormalities, and such drug-induced liver injuries are mainly monitored by measuring blood levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), whereas alpha-glutathione-S-transferase (α-GST) is not routinely measured in clinics, even though it can serve as an earlier and more specific biomarker of liver damage. Susceptibility to drug-induced liver injury can much depend on the gene polymorphisms regulating the activity of DNA detoxification and repair enzymes. The aim of this study was to evaluate which of the three liver enzymes - α-GST, ALT, and AST - is the most sensitive biomarker of olanzapine-induced liver injury and how their blood levels are affected by the GSTT1 , GSTM1 , GSTP1, and OGG1 gene polymorphisms in 30 olanzapine-treated patients. Contrary to our hypothesis, the increase in serum α-GST levels was not significantly greater than that of the transaminases. ALT turned out to be an earlier biomarker of liver injury than the other two enzymes. No significant association was found between gene polymorphisms and liver enzyme levels, save for GSTP1 Ile/Val + Val/Val and ALT, which points to this genotype as a risk factor for drug-induced liver injury. Future studies might help to identify the underlying mechanisms of transient liver enzyme increase associated with this genotype.

Titel:	Are changes in olanzapine-induced liver enzyme levels associated with GSTT1 , GSTM1 , GSTP1 , and OGG1 gene polymorphisms?
Autor/in / Beteiligte Person:	Elkama, A ; İlik, N ; Ak, M ; Karahalil, B
Link:	Full Text Finder (Volltext)
Zeitschrift:	Arhiv za higijenu rada i toksikologiju, Jg. 75 (2024-03-29), Heft 1, S. 61-67
Veröffentlichung:	<2016>- : Zagreb, Croatia : Institut za medicinska istraz̆ivanja i medicinu rada ; <i>Original Publication</i>: Zagreb, Croatia : Institute for Medical Research and Occupational Health, 2024
Medientyp:	academicJournal
ISSN:	1848-6312 (electronic)
DOI:	10.2478/aiht-2024-75-3770
Schlagwort:	Humans Olanzapine Glutathione Transferase genetics Glutathione S-Transferase pi genetics Risk Factors Biomarkers Case-Control Studies Genetic Predisposition to Disease Polymorphism, Genetic Chemical and Drug Induced Liver Injury genetics
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Arh Hig Rada Toksikol] 2024 Mar 29; Vol. 75 (1), pp. 61-67. <i>Date of Electronic Publication: </i>2024 Mar 29 (<i>Print Publication: </i>2024). MeSH Terms: Polymorphism, Genetic* ; Chemical and Drug Induced Liver Injury* / genetics ; Humans ; Olanzapine ; Glutathione Transferase / genetics ; Glutathione S-Transferase pi / genetics ; Risk Factors ; Biomarkers ; Case-Control Studies ; Genetic Predisposition to Disease References: J Hepatol. 2015 Aug;63(2):503-14. (PMID: 25912521) ; Heliyon. 2021 Apr 20;7(4):e06852. (PMID: 33981901) ; Hepatology. 2008 Aug;48(2):588-96. (PMID: 18666253) ; Neuropsychiatr Dis Treat. 2020 Feb 18;16:479-487. (PMID: 32110022) ; Prog Neuropsychopharmacol Biol Psychiatry. 2006 Aug 30;30(6):1163-6. (PMID: 16632162) ; Chin Med. 2021 Dec 11;16(1):135. (PMID: 34895294) ; Encephale. 2002 Nov-Dec;28(6 Pt 1):542-51. (PMID: 12506267) ; Arch Toxicol. 2005 Jul;79(7):377-80. (PMID: 15834708) ; Hong Kong Med J. 2009 Oct;15(5):394-6. (PMID: 19801701) ; J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Oct 15;907:101-7. (PMID: 23026228) ; Am J Psychiatry. 2007 Oct;164(10):1547-56. (PMID: 17898346) ; Int J Neuropsychopharmacol. 2011 Sep;14(8):1069-74. (PMID: 21733244) ; Toxicol Pathol. 2002 May-Jun;30(3):365-72. (PMID: 12051554) ; US Gastroenterol Hepatol Rev. 2010 Jan 1;6:73-80. (PMID: 21874146) ; Psychiatr Danub. 2011 Sep;23 Suppl 1:S15-7. (PMID: 21894094) ; PLoS One. 2017 Aug 24;12(8):e0183812. (PMID: 28837637) ; Gastroenterology Res. 2011 Feb;4(1):13-19. (PMID: 27957007) ; Toxicol Res (Camb). 2022 Jun 01;11(3):547-556. (PMID: 35782649) ; Int J Mol Sci. 2015 Aug 19;16(8):19602-11. (PMID: 26295386) ; Behav Res Methods. 2007 May;39(2):175-91. (PMID: 17695343) ; Toxicol Ind Health. 2014 Oct;30(9):814-25. (PMID: 23081862) ; Prog Neuropsychopharmacol Biol Psychiatry. 2007 Aug 15;31(6):1255-60. (PMID: 17600607) ; Can J Gastroenterol Hepatol. 2019 Oct 20;2019:5850787. (PMID: 31772928) ; J Appl Lab Med. 2016 Sep 1;1(2):119-128. (PMID: 33626782) ; Psychiatry Res. 2010 May 15;177(1-2):268-9. (PMID: 20304505) ; Can J Psychiatry. 2003 Apr;48(3):210. (PMID: 12728748) ; Gene. 2012 Aug 15;505(1):121-7. (PMID: 22652274) ; Front Pharmacol. 2020 Jan 30;10:1667. (PMID: 32082163) ; World J Hepatol. 2021 Jun 27;13(6):620-633. (PMID: 34239698) Contributed Indexing: Keywords: ALT; AST; drug-induced liver injury; lijekom prouzročeno oštećenje jetre; mental disorders; mentalni poremećaji; psihotropni lijekovi; psychotropic drugs; α-GST ; Local Abstract: [Publisher, Croatian] Liječenje olanzapinom može dovesti do prolaznih abnormalnosti u jetrenim biokemijskim nalazima i takva se lijekom prouzročena oštećenja jetre obično nadziru mjerenjem razina alanin aminotransferaze (ALT) i aspartat aminotransferaze (AST) u krvi, a alfa-glutation-S-transferaza (α-GST) ne mjeri se rutinski u klinici premda može poslužiti kao raniji i specifičniji biomarker oštećenja jetre. Osjetljivost jetre na lijekove može dosta ovisiti o polimorfizmu gena regulatora aktivnosti enzima uključenih u procese detoksifikacije i popravka DNA. Cilj je ovoga istraživanja bio ocijeniti koji je od triju jetrenih enzima – α-GST, ALT i AST – najosjetljiviji biomarker olanzapinom prouzročenog oštećenja jetre te kako polimorfizmi gena GSTT1 , GSTM1 , GSTP1 i OGG1 utječu na njihove razine u 30 bolesnika koji su primali taj lijek. Suprotno našoj hipotezi, povišenje serumskih razina α-GST-a nije bilo značajno više od povišenja razina transaminaza. ALT se pokazao ranijim biomarkerom oštećenja jetre od ostalih dvaju enzima. Osim toga, nismo otkrili značajnu povezanost između genskih polimorfizama i razina enzima, izuzev za povezanost genotipa GSTP1 Ile/Val + Val/Val s ALT-om, što upozorava na povećani rizik od lijekom prouzročenog oštećenja jetre u nositelja ovoga genotipa. Buduća bi istraživanja mogla pomoći u prepoznavanju mehanizama uslijed kojih dolazi do prolaznog povišenja razina ovog jetrenog enzima povezanoga s ovim genotipom. Substance Nomenclature: N7U69T4SZR (Olanzapine) ; EC 2.5.1.18 (Glutathione Transferase) ; EC 2.5.1.18 (Glutathione S-Transferase pi) ; 0 (Biomarkers) ; EC 2.5.1.18 (GSTP1 protein, human) Entry Date(s): Date Created: 20240328 Date Completed: 20240401 Latest Revision: 20240401 Update Code: 20240401 PubMed Central ID: PMC10978158

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Are changes in olanzapine-induced liver enzyme levels associated with GSTT1 , GSTM1 , GSTP1 , and OGG1 gene polymorphisms?