The role of glutathione transferase polymorphism in susceptibility to disease

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The role of glutathione transferase polymorphism in susceptibility to disease (en)
Значај полиморфизма глутатион трансфераза у подложности за настанак обољења (sr)
Značaj polimorfizma glutation transferaza u podložnosti za nastanak oboljenja (sr_RS)
Authors

Publications

Association of Nrf2, SOD2 and GPX1 Polymorphisms with Biomarkers of Oxidative Distress and Survival in End-Stage Renal Disease Patients

Jerotić, Đurđa; Matić, Marija; Suvakov, Sonja; Vučićević, Katarina; Damnjanović, Tatjana; Savić-Radojević, Ana; Plješa-Ercegovac, Marija; Ćorić, Vesna; Stefanović, Aleksandra; Ivanišević, Jasmina; Jelić-Ivanović, Zorana; McClements, Lana; Dimković, Nada; Simić, Tatjana

(MDPI, 2019)

TY  - JOUR
AU  - Jerotić, Đurđa
AU  - Matić, Marija
AU  - Suvakov, Sonja
AU  - Vučićević, Katarina
AU  - Damnjanović, Tatjana
AU  - Savić-Radojević, Ana
AU  - Plješa-Ercegovac, Marija
AU  - Ćorić, Vesna
AU  - Stefanović, Aleksandra
AU  - Ivanišević, Jasmina
AU  - Jelić-Ivanović, Zorana
AU  - McClements, Lana
AU  - Dimković, Nada
AU  - Simić, Tatjana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4825
AB  - The oxidative stress response via Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) interlinks inflammation- and metabolism-related pathways in chronic kidney disease. We assessed the association between polymorphisms in Nrf2, superoxide dismutase (SOD2), glutathione peroxidase (GPX1), and the risk of end-stage renal disease (ESRD). The modifying effect of these polymorphisms on both oxidative phenotype and ESRD prognosis, both independently and/or in combination with the glutathione S-transferase M1 (GSTM1) deletion polymorphism, was further analyzed. Polymorphisms in Nrf2 (rs6721961), SOD2 (rs4880), GPX1 (rs1050450), and GSTM1 were determined by PCR in 256 ESRD patients undergoing hemodialysis and 374 controls. Byproducts of oxidative stress were analyzed spectrophotometically or by ELISA. Time-to-event modeling was performed to evaluate overall survival and cardiovascular survival. The SOD2 Val/Val genotype increased ESRD risk (OR = 2.01, p = 0.002), which was even higher in combination with the GPX1 Leu/Leu genotype (OR = 3.27, p = 0.019). Polymorphism in SOD2 also showed an effect on oxidative phenotypes. Overall survival in ESRD patients was dependent on a combination of the Nrf2 (C/C) and GPX1 (Leu/Leu) genotypes in addition to a patients’ age and GSTM1 polymorphism. Similarly, the GPX1 (Leu/Leu) genotype contributed to longer cardiovascular survival. Conclusions: Our results show that SOD2, GPX1, and Nrf2 polymorphisms are associated with ESRD development and can predict survival.
PB  - MDPI
T2  - Toxins
T1  - Association of Nrf2, SOD2 and GPX1 Polymorphisms
with Biomarkers of Oxidative Distress and Survival
in End-Stage Renal Disease Patients
VL  - 11
IS  - 7
DO  - 10.3390/toxins11070431
ER  - 
@article{
author = "Jerotić, Đurđa and Matić, Marija and Suvakov, Sonja and Vučićević, Katarina and Damnjanović, Tatjana and Savić-Radojević, Ana and Plješa-Ercegovac, Marija and Ćorić, Vesna and Stefanović, Aleksandra and Ivanišević, Jasmina and Jelić-Ivanović, Zorana and McClements, Lana and Dimković, Nada and Simić, Tatjana",
year = "2019",
abstract = "The oxidative stress response via Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) interlinks inflammation- and metabolism-related pathways in chronic kidney disease. We assessed the association between polymorphisms in Nrf2, superoxide dismutase (SOD2), glutathione peroxidase (GPX1), and the risk of end-stage renal disease (ESRD). The modifying effect of these polymorphisms on both oxidative phenotype and ESRD prognosis, both independently and/or in combination with the glutathione S-transferase M1 (GSTM1) deletion polymorphism, was further analyzed. Polymorphisms in Nrf2 (rs6721961), SOD2 (rs4880), GPX1 (rs1050450), and GSTM1 were determined by PCR in 256 ESRD patients undergoing hemodialysis and 374 controls. Byproducts of oxidative stress were analyzed spectrophotometically or by ELISA. Time-to-event modeling was performed to evaluate overall survival and cardiovascular survival. The SOD2 Val/Val genotype increased ESRD risk (OR = 2.01, p = 0.002), which was even higher in combination with the GPX1 Leu/Leu genotype (OR = 3.27, p = 0.019). Polymorphism in SOD2 also showed an effect on oxidative phenotypes. Overall survival in ESRD patients was dependent on a combination of the Nrf2 (C/C) and GPX1 (Leu/Leu) genotypes in addition to a patients’ age and GSTM1 polymorphism. Similarly, the GPX1 (Leu/Leu) genotype contributed to longer cardiovascular survival. Conclusions: Our results show that SOD2, GPX1, and Nrf2 polymorphisms are associated with ESRD development and can predict survival.",
publisher = "MDPI",
journal = "Toxins",
title = "Association of Nrf2, SOD2 and GPX1 Polymorphisms
with Biomarkers of Oxidative Distress and Survival
in End-Stage Renal Disease Patients",
volume = "11",
number = "7",
doi = "10.3390/toxins11070431"
}
Jerotić, Đ., Matić, M., Suvakov, S., Vučićević, K., Damnjanović, T., Savić-Radojević, A., Plješa-Ercegovac, M., Ćorić, V., Stefanović, A., Ivanišević, J., Jelić-Ivanović, Z., McClements, L., Dimković, N.,& Simić, T.. (2019). Association of Nrf2, SOD2 and GPX1 Polymorphisms
with Biomarkers of Oxidative Distress and Survival
in End-Stage Renal Disease Patients. in Toxins
MDPI., 11(7).
https://doi.org/10.3390/toxins11070431
Jerotić Đ, Matić M, Suvakov S, Vučićević K, Damnjanović T, Savić-Radojević A, Plješa-Ercegovac M, Ćorić V, Stefanović A, Ivanišević J, Jelić-Ivanović Z, McClements L, Dimković N, Simić T. Association of Nrf2, SOD2 and GPX1 Polymorphisms
with Biomarkers of Oxidative Distress and Survival
in End-Stage Renal Disease Patients. in Toxins. 2019;11(7).
doi:10.3390/toxins11070431 .
Jerotić, Đurđa, Matić, Marija, Suvakov, Sonja, Vučićević, Katarina, Damnjanović, Tatjana, Savić-Radojević, Ana, Plješa-Ercegovac, Marija, Ćorić, Vesna, Stefanović, Aleksandra, Ivanišević, Jasmina, Jelić-Ivanović, Zorana, McClements, Lana, Dimković, Nada, Simić, Tatjana, "Association of Nrf2, SOD2 and GPX1 Polymorphisms
with Biomarkers of Oxidative Distress and Survival
in End-Stage Renal Disease Patients" in Toxins, 11, no. 7 (2019),
https://doi.org/10.3390/toxins11070431 . .
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Markers of Oxidative Stress and Endothelial Dysfunction Predict Haemodialysis Patients Survival

Šuvakov, Sonja; Jerotić, D; Damjanović, Tatjana; Milić, N; Pekmezović, T; Đukić, Tatjana; Jelić-Ivanović, Zorana; Savić-Radojević, Ana; Pljesa-Ercegovac, Marija; Matić, Marija; McClements, L; Dimković, Nada; Garović, V.D; Albright, R.C; Simić, Tatjana

(S. Karger AG, 2019)

TY  - JOUR
AU  - Šuvakov, Sonja
AU  - Jerotić, D
AU  - Damjanović, Tatjana
AU  - Milić, N
AU  - Pekmezović, T
AU  - Đukić, Tatjana
AU  - Jelić-Ivanović, Zorana
AU  - Savić-Radojević, Ana
AU  - Pljesa-Ercegovac, Marija
AU  - Matić, Marija
AU  - McClements, L
AU  - Dimković, Nada
AU  - Garović, V.D
AU  - Albright, R.C
AU  - Simić, Tatjana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3277
AB  - Introduction: Overall survival of patients with end-stage renal disease (ESRD) remains poor. Oxidative stress is one of the major risk factors associated with mortality in this patient group. As glutathione S-transferases (GST) are well-established antioxidants, we hypothesized that a model including GST gene polymorphisms, oxidative damage byproducts and cell adhesion markers has a prognostic role in ESRD patient survival. Methods: A prospective study of 199 patients with ESRD on haemodialysis was conducted. GST genotype, oxidative stress byproducts and cell adhesion molecules were measured in plasma. Multivariate Cox regression and Kaplan-Meier survival analyses were performed to test the predictive ability of these parameters in the 8-year follow-up period. Results: GSTM1-null genotype was associated with significantly shorter overall (HR 1.6, p = 0.018) and cardiovascular-specific (HR 2.1, p = 0.010) survival. Oxidative stress byproducts (advanced oxidation protein products [AOPP], prooxidant-antioxidant balance [PAB], malondialdehyde [MDA]) and cell adhesion molecules (soluble vascular cell adhesion molecule-1 [sVCAM-1] and soluble intercellular adhesion molecule-1 [sICAM-1]) demonstrated a significant predictive role in terms of overall and cardiovascular survival. When 6 biomarkers (GSTM1 genotype, high AOPP/PAB/MDA/-sVCAM-1/sICAM-1) were combined into a scoring model, a significantly shorter overall and cardiovascular survival was observed for patients with the highest score (p  lt  0.001). Conclusion: We identified a novel panel of biomarkers that can be utilized in predicting survival in ESRD patients. This biomarker signature could enable better monitoring of patients and stratification into appropriate treatment groups.
PB  - S. Karger AG
T2  - American Journal of Nephrology
T1  - Markers of Oxidative Stress and Endothelial Dysfunction Predict Haemodialysis Patients Survival
DO  - 10.1159/000501300
ER  - 
@article{
author = "Šuvakov, Sonja and Jerotić, D and Damjanović, Tatjana and Milić, N and Pekmezović, T and Đukić, Tatjana and Jelić-Ivanović, Zorana and Savić-Radojević, Ana and Pljesa-Ercegovac, Marija and Matić, Marija and McClements, L and Dimković, Nada and Garović, V.D and Albright, R.C and Simić, Tatjana",
year = "2019",
abstract = "Introduction: Overall survival of patients with end-stage renal disease (ESRD) remains poor. Oxidative stress is one of the major risk factors associated with mortality in this patient group. As glutathione S-transferases (GST) are well-established antioxidants, we hypothesized that a model including GST gene polymorphisms, oxidative damage byproducts and cell adhesion markers has a prognostic role in ESRD patient survival. Methods: A prospective study of 199 patients with ESRD on haemodialysis was conducted. GST genotype, oxidative stress byproducts and cell adhesion molecules were measured in plasma. Multivariate Cox regression and Kaplan-Meier survival analyses were performed to test the predictive ability of these parameters in the 8-year follow-up period. Results: GSTM1-null genotype was associated with significantly shorter overall (HR 1.6, p = 0.018) and cardiovascular-specific (HR 2.1, p = 0.010) survival. Oxidative stress byproducts (advanced oxidation protein products [AOPP], prooxidant-antioxidant balance [PAB], malondialdehyde [MDA]) and cell adhesion molecules (soluble vascular cell adhesion molecule-1 [sVCAM-1] and soluble intercellular adhesion molecule-1 [sICAM-1]) demonstrated a significant predictive role in terms of overall and cardiovascular survival. When 6 biomarkers (GSTM1 genotype, high AOPP/PAB/MDA/-sVCAM-1/sICAM-1) were combined into a scoring model, a significantly shorter overall and cardiovascular survival was observed for patients with the highest score (p  lt  0.001). Conclusion: We identified a novel panel of biomarkers that can be utilized in predicting survival in ESRD patients. This biomarker signature could enable better monitoring of patients and stratification into appropriate treatment groups.",
publisher = "S. Karger AG",
journal = "American Journal of Nephrology",
title = "Markers of Oxidative Stress and Endothelial Dysfunction Predict Haemodialysis Patients Survival",
doi = "10.1159/000501300"
}
Šuvakov, S., Jerotić, D., Damjanović, T., Milić, N., Pekmezović, T., Đukić, T., Jelić-Ivanović, Z., Savić-Radojević, A., Pljesa-Ercegovac, M., Matić, M., McClements, L., Dimković, N., Garović, V.D, Albright, R.C,& Simić, T.. (2019). Markers of Oxidative Stress and Endothelial Dysfunction Predict Haemodialysis Patients Survival. in American Journal of Nephrology
S. Karger AG..
https://doi.org/10.1159/000501300
Šuvakov S, Jerotić D, Damjanović T, Milić N, Pekmezović T, Đukić T, Jelić-Ivanović Z, Savić-Radojević A, Pljesa-Ercegovac M, Matić M, McClements L, Dimković N, Garović V, Albright R, Simić T. Markers of Oxidative Stress and Endothelial Dysfunction Predict Haemodialysis Patients Survival. in American Journal of Nephrology. 2019;.
doi:10.1159/000501300 .
Šuvakov, Sonja, Jerotić, D, Damjanović, Tatjana, Milić, N, Pekmezović, T, Đukić, Tatjana, Jelić-Ivanović, Zorana, Savić-Radojević, Ana, Pljesa-Ercegovac, Marija, Matić, Marija, McClements, L, Dimković, Nada, Garović, V.D, Albright, R.C, Simić, Tatjana, "Markers of Oxidative Stress and Endothelial Dysfunction Predict Haemodialysis Patients Survival" in American Journal of Nephrology (2019),
https://doi.org/10.1159/000501300 . .
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Glutathione S-transferase A1, M1, P1 and T1 null or low-activity genotypes are associated with enhanced oxidative damage among haemodialysis patients

Šuvakov, Sonja; Damjanović, Tatjana; Stefanović, Aleksandra; Pekmezović, Tatjana; Savić-Radojević, Ana; Pljesa-Ercegovac, Marija; Matić, Marija; Đukić, Tatjana; Corić, Vesna; Jakovljević, Jovana; Ivanišević, Jasmina; Plješa, Steva; Jelić-Ivanović, Zorana; Mimić-Oka, Jasmina; Dimković, Nada; Simić, Tatjana

(Oxford Univ Press, Oxford, 2013)

TY  - JOUR
AU  - Šuvakov, Sonja
AU  - Damjanović, Tatjana
AU  - Stefanović, Aleksandra
AU  - Pekmezović, Tatjana
AU  - Savić-Radojević, Ana
AU  - Pljesa-Ercegovac, Marija
AU  - Matić, Marija
AU  - Đukić, Tatjana
AU  - Corić, Vesna
AU  - Jakovljević, Jovana
AU  - Ivanišević, Jasmina
AU  - Plješa, Steva
AU  - Jelić-Ivanović, Zorana
AU  - Mimić-Oka, Jasmina
AU  - Dimković, Nada
AU  - Simić, Tatjana
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1949
AB  - Background. Increased oxidative stress is a hallmark of end-stage renal disease (ESRD). Glutathione S-transferases (GST) are involved in the detoxification of xenobiotics and protection of oxidative damage. We hypothesized that genetic polymorphism in antioxidant enzymes GSTA1, GSTM1, GSTP1 and GSTT1 is more frequent in ESRD and modulates the degree of oxidative stress in these patients. Methods. GSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 199 ESRD patients and 199 age- and gender-matched controls. Markers of protein and lipid oxidative damage [thiol groups, carbonyl groups, advanced oxidative protein products, nitrotyrosine, malondialdehyde (MDA) and MDA adducts], together with total oxidant status and pro-oxidant antioxidant balance were determined. Results. Individual GST polymorphisms influence vulnerability to both protein and lipid oxidation, with GSTM1-null gene variant having the most pronounced effect. Furthermore, a strong combined effect of null/low-activity GSTM1, GSM, GSTA1 and GSTP1 genotypes in terms of susceptibility towards oxidative and carbonyl stress was found in ESRD patients. When patients were stratified according to GSTM1 and GSTT1, the highest oxidant damage was noted in those with the GSTM1-null/GSTT1-null genotype. The observed effect was even stronger in patients with the third low-activity GSTP1 or GSTA1 genotype. Finally, the level of oxidative and carbonyl stress was most pronounced in the subgroup of patients with all four null or low-activity GSTM1, GSTT1, GSTP1 and GSTA1 genotypes. Conclusions. According to the GST genotype, ESRD patients may be stratified in terms of the level of oxidative and carbonyl stress that might influence cardiovascular prognosis, but could also improve efforts towards individualization of antioxidant treatment.
PB  - Oxford Univ Press, Oxford
T2  - Nephrology Dialysis Transplantation
T1  - Glutathione S-transferase A1, M1, P1 and T1 null or low-activity genotypes are associated with enhanced oxidative damage among haemodialysis patients
VL  - 28
IS  - 1
SP  - 202
EP  - 212
DO  - 10.1093/ndt/gfs369
ER  - 
@article{
author = "Šuvakov, Sonja and Damjanović, Tatjana and Stefanović, Aleksandra and Pekmezović, Tatjana and Savić-Radojević, Ana and Pljesa-Ercegovac, Marija and Matić, Marija and Đukić, Tatjana and Corić, Vesna and Jakovljević, Jovana and Ivanišević, Jasmina and Plješa, Steva and Jelić-Ivanović, Zorana and Mimić-Oka, Jasmina and Dimković, Nada and Simić, Tatjana",
year = "2013",
abstract = "Background. Increased oxidative stress is a hallmark of end-stage renal disease (ESRD). Glutathione S-transferases (GST) are involved in the detoxification of xenobiotics and protection of oxidative damage. We hypothesized that genetic polymorphism in antioxidant enzymes GSTA1, GSTM1, GSTP1 and GSTT1 is more frequent in ESRD and modulates the degree of oxidative stress in these patients. Methods. GSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 199 ESRD patients and 199 age- and gender-matched controls. Markers of protein and lipid oxidative damage [thiol groups, carbonyl groups, advanced oxidative protein products, nitrotyrosine, malondialdehyde (MDA) and MDA adducts], together with total oxidant status and pro-oxidant antioxidant balance were determined. Results. Individual GST polymorphisms influence vulnerability to both protein and lipid oxidation, with GSTM1-null gene variant having the most pronounced effect. Furthermore, a strong combined effect of null/low-activity GSTM1, GSM, GSTA1 and GSTP1 genotypes in terms of susceptibility towards oxidative and carbonyl stress was found in ESRD patients. When patients were stratified according to GSTM1 and GSTT1, the highest oxidant damage was noted in those with the GSTM1-null/GSTT1-null genotype. The observed effect was even stronger in patients with the third low-activity GSTP1 or GSTA1 genotype. Finally, the level of oxidative and carbonyl stress was most pronounced in the subgroup of patients with all four null or low-activity GSTM1, GSTT1, GSTP1 and GSTA1 genotypes. Conclusions. According to the GST genotype, ESRD patients may be stratified in terms of the level of oxidative and carbonyl stress that might influence cardiovascular prognosis, but could also improve efforts towards individualization of antioxidant treatment.",
publisher = "Oxford Univ Press, Oxford",
journal = "Nephrology Dialysis Transplantation",
title = "Glutathione S-transferase A1, M1, P1 and T1 null or low-activity genotypes are associated with enhanced oxidative damage among haemodialysis patients",
volume = "28",
number = "1",
pages = "202-212",
doi = "10.1093/ndt/gfs369"
}
Šuvakov, S., Damjanović, T., Stefanović, A., Pekmezović, T., Savić-Radojević, A., Pljesa-Ercegovac, M., Matić, M., Đukić, T., Corić, V., Jakovljević, J., Ivanišević, J., Plješa, S., Jelić-Ivanović, Z., Mimić-Oka, J., Dimković, N.,& Simić, T.. (2013). Glutathione S-transferase A1, M1, P1 and T1 null or low-activity genotypes are associated with enhanced oxidative damage among haemodialysis patients. in Nephrology Dialysis Transplantation
Oxford Univ Press, Oxford., 28(1), 202-212.
https://doi.org/10.1093/ndt/gfs369
Šuvakov S, Damjanović T, Stefanović A, Pekmezović T, Savić-Radojević A, Pljesa-Ercegovac M, Matić M, Đukić T, Corić V, Jakovljević J, Ivanišević J, Plješa S, Jelić-Ivanović Z, Mimić-Oka J, Dimković N, Simić T. Glutathione S-transferase A1, M1, P1 and T1 null or low-activity genotypes are associated with enhanced oxidative damage among haemodialysis patients. in Nephrology Dialysis Transplantation. 2013;28(1):202-212.
doi:10.1093/ndt/gfs369 .
Šuvakov, Sonja, Damjanović, Tatjana, Stefanović, Aleksandra, Pekmezović, Tatjana, Savić-Radojević, Ana, Pljesa-Ercegovac, Marija, Matić, Marija, Đukić, Tatjana, Corić, Vesna, Jakovljević, Jovana, Ivanišević, Jasmina, Plješa, Steva, Jelić-Ivanović, Zorana, Mimić-Oka, Jasmina, Dimković, Nada, Simić, Tatjana, "Glutathione S-transferase A1, M1, P1 and T1 null or low-activity genotypes are associated with enhanced oxidative damage among haemodialysis patients" in Nephrology Dialysis Transplantation, 28, no. 1 (2013):202-212,
https://doi.org/10.1093/ndt/gfs369 . .
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