Glutathione S-transferase A1, M1, P1 and T1 null or low-activity genotypes are associated with enhanced oxidative damage among haemodialysis patients
2013
Authors
Šuvakov, SonjaDamjanović, 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
Article (Published version)
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Show full item recordAbstract
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 G...STM1, 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.
Keywords:
end-stage renal disease / glutathione S-transferases / haemodialysis / oxidative stress / polymorphismSource:
Nephrology Dialysis Transplantation, 2013, 28, 1, 202-212Publisher:
- Oxford Univ Press, Oxford
Funding / projects:
- The role of glutathione transferase polymorphism in susceptibility to disease (RS-MESTD-Basic Research (BR or ON)-175052)
DOI: 10.1093/ndt/gfs369
ISSN: 0931-0509
PubMed: 23034843
WoS: 000315540100034
Scopus: 2-s2.0-84872228525
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PharmacyTY - 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 . .