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Expression Levels of GABA-A Receptor Subunit Alpha 3, Gabra3 and Lipoprotein Lipase, Lpl Are Associated with the Susceptibility to Acetaminophen-Induced Hepatotoxicity

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dc.contributor.author남기택-
dc.date.accessioned2017-11-02T08:39:04Z-
dc.date.available2017-11-02T08:39:04Z-
dc.date.issued2017-
dc.identifier.issn1976-9148-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/154717-
dc.description.abstractDrug-induced liver injury (DILI) is the serious and fatal drug-associated adverse effect, but its incidence is very low and individual variation in severity is substantial. Acetaminophen (APAP)-induced liver injury accounts for >50% of reported DILI cases but little is known for the cause of individual variations in the severity. Intrinsic genetic variation is considered a key element but the identity of the genes was not well-established. Here, pre-biopsy method and microarray technique was applied to uncover the key genes for APAP-induced liver injury in mice, and a cause and effect experiment employing quantitative real-time PCR was conducted to confirm the correlation between the uncovered genes and APAP-induced hepatotoxicity. We identified the innately and differentially expressed genes of mice susceptible to APAP-induced hepatotoxicity in the pre-biopsied liver tissue before APAP treatment through microarray analysis of the global gene expression profiles (Affymetrix GeneChip® Mouse Gene 1.0 ST for 28,853 genes). Expression of 16 genes including Gdap10, Lpl, Gabra3 and Ccrn4l were significantly different (t-test: FDR <10%) more than 1.5 fold in the susceptible animals than resistant. To confirm the association with the susceptibility to APAP-induced hepatotoxicity, another set of animals were measured for the expression level of selected 4 genes (higher two and lower two genes) in the liver pre-biopsy and their sensitivity to APAP-induced hepatotoxicity was evaluated by post hoc. Notably, the expressions of Gabra3 and Lpl were significantly correlated with the severity of liver injury (p<0.05) demonstrating that these genes may be linked to the susceptibility to APAP-induced hepatotoxicity.-
dc.description.statementOfResponsibilityopen-
dc.languageKorean-
dc.publisherKorean Society of Applied Pharmacology-
dc.relation.isPartOfBIOMOLECULES & THERAPEUTICS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleExpression Levels of GABA-A Receptor Subunit Alpha 3, Gabra3 and Lipoprotein Lipase, Lpl Are Associated with the Susceptibility to Acetaminophen-Induced Hepatotoxicity-
dc.typeArticle-
dc.publisher.locationKorea-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Life Science-
dc.contributor.googleauthorMinjeong Kim-
dc.contributor.googleauthorJun-Won Yun-
dc.contributor.googleauthorKyeho Shin-
dc.contributor.googleauthorYejin Cho-
dc.contributor.googleauthorMijeong Yang-
dc.contributor.googleauthorKi Taek Nam-
dc.contributor.googleauthorKyung-Min Lim-
dc.identifier.doi10.4062/biomolther.2016.076.-
dc.contributor.localIdA01243-
dc.relation.journalcodeJ00324-
dc.identifier.eissn2005-4483-
dc.relation.journalsince2008~-
dc.identifier.pmid27530116-
dc.relation.journalbefore~2007 Journal of Applied Pharmacology-
dc.subject.keywordAcetaminophen-
dc.subject.keywordGABA-A receptor subunit alpha 3-
dc.subject.keywordHepatotoxicity-
dc.subject.keywordLipoprotein lipase-
dc.subject.keywordToxicogenomics-
dc.contributor.alternativeNameNam, Ki Taek-
dc.contributor.affiliatedAuthorNam, Ki Taek-
dc.citation.titleBiomolecules & Therapeutics-
dc.citation.volume25-
dc.citation.number2-
dc.citation.startPage112-
dc.citation.endPage121-
dc.identifier.bibliographicCitationBIOMOLECULES & THERAPEUTICS, Vol.25(2) : 112-121, 2017-
dc.date.modified2017-11-01-
dc.identifier.rimsid44198-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers

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