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dc.creatorReljic, Zorica
dc.creatorZlatović, Mario
dc.creatorSavic-Radojevic, Ana
dc.creatorPekmezovic, Tatjana
dc.creatorDjukanovic, Ljubica
dc.creatorMatic, Marija
dc.creatorPljesa-Ercegovac, Marija
dc.creatorMimic-Oka, Jasmina
dc.creatorOpsenica, Dejan
dc.creatorSimić, Tatjana
dc.date.accessioned2019-01-30T17:39:12Z
dc.date.available2019-01-30T17:39:12Z
dc.date.issued2014
dc.identifier.issn2072-6651
dc.identifier.urihttp://cer.ihtm.bg.ac.rs/handle/123456789/1417
dc.description.abstractAlthough recent data suggest aristolochic acid as a putative cause of Balkan endemic nephropathy (BEN), evidence also exists in favor of ochratoxin A (OTA) exposure as risk factor for the disease. The potential role of xenobiotic metabolizing enzymes, such as the glutathione transferases (GSTs), in OTA biotransformation is based on OTA glutathione adducts (OTHQ-SG and OTB-SG) in blood and urine of BEN patients. We aimed to analyze the association between common GSTA1, GSTM1, GSTT1, and GSTP1 polymorphisms and BEN susceptibility, and thereafter performed an in silico simulation of particular GST enzymes potentially involved in OTA transformations. GSTA1, GSTM1, GSTT1 and GSTP1 genotypes were determined in 207 BEN patients and 138 non-BEN healthy individuals from endemic regions by polymerase chain reaction (PCR). Molecular modeling in silico was performed for GSTA1 protein. Among the GST polymorphisms tested, only GSTA1 was significantly associated with a higher risk of BEN. Namely, carriers of the GSTA1*B gene variant, associated with lower transcriptional activation, were at a 1.6-fold higher BEN risk than those carrying the homozygous GSTA1*A/*A genotype (OR = 1.6; p = 0.037). In in silico modeling, we found four structures, two OTB-SG and two OTHQ-SG, bound in a GSTA1 monomer. We found that GSTA1 polymorphism was associated with increased risk of BEN, and suggested, according to the in silico simulation, that GSTA1-1 might be involved in catalyzing the formation of OTHQ-SG and OTB-SG conjugates.en
dc.publisherMdpi Ag, Basel
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175052/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172008/RS//
dc.rightsopenAccess
dc.sourceToxins
dc.subjectBalkan endemic nephropathyen
dc.subjectbiotransformationen
dc.subjectglutathione transferase A1en
dc.subjectochratoxin Aen
dc.subjectpolymorphismen
dc.titleIs Increased Susceptibility to Balkan Endemic Nephropathy in Carriers of Common GSTA1 (*A/*B) Polymorphism Linked with the Catalytic Role of GSTA1 in Ochratoxin A Biotransformation? Serbian Case Control Study and In Silico Analysisen
dc.typearticle
dc.rights.licenseBY
dcterms.abstractДјукановиц, Љубица; Опсеница, Дејан; Златовиц, Марио; Симиц, Татјана; Савиц-Радојевиц, Aна; Мимиц-Ока, Јасмина; Пљеса-Ерцеговац, Марија; Матиц, Марија; Рељиц, Зорица; Пекмезовиц, Татјана;
dc.citation.volume6
dc.citation.issue8
dc.citation.spage2348
dc.citation.epage2362
dc.citation.other6(8): 2348-2362
dc.citation.rankM22
dc.identifier.pmid25111321
dc.identifier.doi10.3390/toxins6082348
dc.identifier.rcubConv_3211
dc.identifier.fulltexthttp://cer.ihtm.bg.ac.rs//bitstream/id/7898/1415.pdf
dc.identifier.scopus2-s2.0-84926072748
dc.identifier.wos000341427200009
dc.type.versionpublishedVersion


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