TY  - JOUR
AU  - Reljic, Zorica
AU  - Zlatović, Mario
AU  - Savic-Radojevic, Ana
AU  - Pekmezovic, Tatjana
AU  - Djukanovic, Ljubica
AU  - Matic, Marija
AU  - Pljesa-Ercegovac, Marija
AU  - Mimic-Oka, Jasmina
AU  - Opsenica, Dejan M.
AU  - Simić, Tatjana
PY  - 2014
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1842
AB  - Although 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.
PB  - Mdpi Ag, Basel
T2  - Toxins
T1  - Is 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 Analysis
VL  - 6
IS  - 8
SP  - 2348
EP  - 2362
DO  - 10.3390/toxins6082348
ER  - 

@article{
author = "Reljic, Zorica and Zlatović, Mario and Savic-Radojevic, Ana and Pekmezovic, Tatjana and Djukanovic, Ljubica and Matic, Marija and Pljesa-Ercegovac, Marija and Mimic-Oka, Jasmina and Opsenica, Dejan M. and Simić, Tatjana",
year = "2014",
abstract = "Although 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.",
publisher = "Mdpi Ag, Basel",
journal = "Toxins",
title = "Is 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 Analysis",
volume = "6",
number = "8",
pages = "2348-2362",
doi = "10.3390/toxins6082348"
}

Reljic, Z., Zlatović, M., Savic-Radojevic, A., Pekmezovic, T., Djukanovic, L., Matic, M., Pljesa-Ercegovac, M., Mimic-Oka, J., Opsenica, D. M.,& Simić, T.. (2014). Is 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 Analysis. in Toxins
Mdpi Ag, Basel., 6(8), 2348-2362.
https://doi.org/10.3390/toxins6082348

Reljic Z, Zlatović M, Savic-Radojevic A, Pekmezovic T, Djukanovic L, Matic M, Pljesa-Ercegovac M, Mimic-Oka J, Opsenica DM, Simić T. Is 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 Analysis. in Toxins. 2014;6(8):2348-2362.
doi:10.3390/toxins6082348 .

Reljic, Zorica, Zlatović, Mario, Savic-Radojevic, Ana, Pekmezovic, Tatjana, Djukanovic, Ljubica, Matic, Marija, Pljesa-Ercegovac, Marija, Mimic-Oka, Jasmina, Opsenica, Dejan M., Simić, Tatjana, "Is 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 Analysis" in Toxins, 6, no. 8 (2014):2348-2362,
https://doi.org/10.3390/toxins6082348 . .