TY  - JOUR
AU  - Grubiša, Ivana
AU  - Otašević, Petar
AU  - Vucinić, Nada
AU  - Miličić, Biljana
AU  - Jozić, Tanja
AU  - Krstić, Slobodan
AU  - Milašin, Jelena
PY  - 2018
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/2287
AB  - Oxidative stress (OS) plays an important role in atherogenesis and since glutathione S-transferases (GSTs) provide protection against OS, we have tested the hypothesis that deletion polymorphisms in two GSTs (GSTM1 and GSTT1) may affect the risk of developing atherosclerosis. A total of 382 individuals (200 patients with atherosclerosis and 182 healthy controls) were included in this association study. Genomic DNA was isolated from peripheral blood cells or from buccal epithelial cells and genotyping was performed using multiplex-PCR or real-time PCR methods. GSTM1 null genotype was significantly more frequent in atherosclerotic patients than in controls (52.0% vs 34.1%) and individuals with the GSTM1 null genotype had an approximately 2-fold increase in atherosclerosis risk (OR: 2.1, 95%CI=1.39-3.17, P=0.0004). GSTT1 null genotype alone did not show a statistically significant effect on atherosclerosis risk modulation, but the association approached significance (OR: 1.57, 95%CI=0.94-2.64, P=0.08). The combined analysis showed that the presence of both genes had a protective effect against atherosclerosis (OR=0.55, 95%CI=0.37-0.83, P=0.005) while double null genotypes led to a robust atherosclerosis risk increase (OR: 8.14, 95%CI=2.41-27.51, P  lt  0.0001). This study demonstrated that the GSTM1 null and combined GSTM1/GSTT1 null genotypes are susceptibility factors for development of atherosclerosis in a Serbian population.
PB  - Soc Brasil Genetica, Ribeirao Pret
T2  - Genetics & Molecular Biology
T1  - Combined GSTM1 and GSTT1 null genotypes are strong risk factors for atherogenesis in a Serbian population
VL  - 41
IS  - 1
SP  - 35
EP  - 40
DO  - 10.1590/1678-4685-GMB-2017-0034
ER  - 

@article{
author = "Grubiša, Ivana and Otašević, Petar and Vucinić, Nada and Miličić, Biljana and Jozić, Tanja and Krstić, Slobodan and Milašin, Jelena",
year = "2018",
abstract = "Oxidative stress (OS) plays an important role in atherogenesis and since glutathione S-transferases (GSTs) provide protection against OS, we have tested the hypothesis that deletion polymorphisms in two GSTs (GSTM1 and GSTT1) may affect the risk of developing atherosclerosis. A total of 382 individuals (200 patients with atherosclerosis and 182 healthy controls) were included in this association study. Genomic DNA was isolated from peripheral blood cells or from buccal epithelial cells and genotyping was performed using multiplex-PCR or real-time PCR methods. GSTM1 null genotype was significantly more frequent in atherosclerotic patients than in controls (52.0% vs 34.1%) and individuals with the GSTM1 null genotype had an approximately 2-fold increase in atherosclerosis risk (OR: 2.1, 95%CI=1.39-3.17, P=0.0004). GSTT1 null genotype alone did not show a statistically significant effect on atherosclerosis risk modulation, but the association approached significance (OR: 1.57, 95%CI=0.94-2.64, P=0.08). The combined analysis showed that the presence of both genes had a protective effect against atherosclerosis (OR=0.55, 95%CI=0.37-0.83, P=0.005) while double null genotypes led to a robust atherosclerosis risk increase (OR: 8.14, 95%CI=2.41-27.51, P  lt  0.0001). This study demonstrated that the GSTM1 null and combined GSTM1/GSTT1 null genotypes are susceptibility factors for development of atherosclerosis in a Serbian population.",
publisher = "Soc Brasil Genetica, Ribeirao Pret",
journal = "Genetics & Molecular Biology",
title = "Combined GSTM1 and GSTT1 null genotypes are strong risk factors for atherogenesis in a Serbian population",
volume = "41",
number = "1",
pages = "35-40",
doi = "10.1590/1678-4685-GMB-2017-0034"
}

Grubiša, I., Otašević, P., Vucinić, N., Miličić, B., Jozić, T., Krstić, S.,& Milašin, J.. (2018). Combined GSTM1 and GSTT1 null genotypes are strong risk factors for atherogenesis in a Serbian population. in Genetics & Molecular Biology
Soc Brasil Genetica, Ribeirao Pret., 41(1), 35-40.
https://doi.org/10.1590/1678-4685-GMB-2017-0034

Grubiša I, Otašević P, Vucinić N, Miličić B, Jozić T, Krstić S, Milašin J. Combined GSTM1 and GSTT1 null genotypes are strong risk factors for atherogenesis in a Serbian population. in Genetics & Molecular Biology. 2018;41(1):35-40.
doi:10.1590/1678-4685-GMB-2017-0034 .

Grubiša, Ivana, Otašević, Petar, Vucinić, Nada, Miličić, Biljana, Jozić, Tanja, Krstić, Slobodan, Milašin, Jelena, "Combined GSTM1 and GSTT1 null genotypes are strong risk factors for atherogenesis in a Serbian population" in Genetics & Molecular Biology, 41, no. 1 (2018):35-40,
https://doi.org/10.1590/1678-4685-GMB-2017-0034 . .

TY  - JOUR
AU  - Grubiša, Ivana
AU  - Otašević, Petar
AU  - Dimković, Nada
AU  - Nedeljković, Ivana
AU  - Toljić, Boško
AU  - Vučinić, Nada
PY  - 2013
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1800
AB  - Introduction. Paraoxonase 1 (PON1) is a multifunctional enzyme associated with high-density lipoprotein particles (HDL). It is a cellular antioxidant that hydrolyses oxidized macromolecules, especially low-density lipoproteins (ox-LDL). Because increased oxidative stress is believed to play a crucial role in the initiation and propagation of atherosclerosis, coding (Q192R and L55M) and promoter (C(-107)T) region polymorphisms of pon1 gene, that are responsible for catalytic efficiency, activity and the level of the enzyme, have been of great interest as a potential markers of susceptibility for atherogenesis. Objective. The aim of the study was to assess possible association between these pon1 gene variants and clinical manifestations of the atherosclerosis and oxidative stress. Methods. A total of 60 angiographically documented patients with manifested atherosclerotic disease and 100 control individuals were analyzed. Genomic DNA was isolated from the peripheral blood cells and genotyping was performed using polymerase chain reaction followed by the restriction fragment length polymorphism (PCR-RFLP) analysis. Results No significant difference in allele and genotype frequencies of all three examined polymorphisms was found between the atherosclerotic patients and healthy controls. The obtained results could not support an association of pon1 gene variants with the oxidative stress and atherogenesis. Conclusion. These polymorphisms cannot be considered risk factors of atherosclerosis in Serbian population. A larger study is required in order to establish possible contribution of pon1 variants to atherosclerosis-related cardiovascular diseases.
AB  - Uvod. Paraoksonaza 1 (PON1) je multifunkcionalni enzim koji je vezan za lipoproteine visoke gustine (HDL). To je ćelijski antioksidans koji hidrolizuje oksidovane makromolekule, naročito oksidovane lipoproteine niske gustine (ox-LDL). Smatra se da povišeni oksidativni stres igra ključnu ulogu u inicijaciji i propagaciji ateroskleroze, pa su polimorfizmi u kodirajućem (Q192R i L55M) i promotorskom (C(-107)T) regionu gena pon1, koji su odgovorni za katalitičku efikasnost, aktivnost i nivo enzima, od velikog interesa kao potencijalni markeri osetljivosti na aterogenezu. Cilj rada. Cilj ove studije je bio da se ispita moguća povezanost varijanti gena pon1 i kliničkih manifestacija ateroskleroze i oksidativnog stresa. Metode rada. Analizirano je 60 bolesnika s angiografski dokumentovanim manifestacijama ateroskleroze i 100 zdravih ispitanika. Genomska DNK je izolovana iz ćelija periferne krvi, a genotipizacija je urađena primenom reakcije lančane polimeraze, posle koje je urađena analiza dužine restrikcionih fragmenata (tzv. PCR-RFLP analiza). Rezultati. Učestalosti alela i genotipova tri ispitivana polimorfizma nisu pokazale značajne razlike između ispitanika obolelih od ateroskleroze i zdravih osoba. Dobijeni rezultati ne ukazuju na povezanost analiziranih varijanti gena pon1 i oksidativnog stresa i aterogeneze. Zaključak. Ovi polimorfizmi se ne mogu smatrati faktorima rizika za razvoj ateroskleroze u srpskoj populaciji. Potrebna je studija sa većim brojem ispitanika, kako bi se utvrdio mogući doprinos varijanti gena pon1 na nastanak kardiovaskularnih oboljenja u čijoj osnovi je ateroskleroza.
PB  - Srpsko lekarsko društvo, Beograd
T2  - Srpski arhiv za celokupno lekarstvo
T1  - Genetic polymorphisms of paraoxonase 1 and susceptibility to atherogenesis
T1  - Genetički polimorfizmi paraoksonaze 1 i podložnost aterogenezi
VL  - 141
IS  - 9-10
SP  - 629
EP  - 633
DO  - 10.2298/SARH1310629G
ER  - 

@article{
author = "Grubiša, Ivana and Otašević, Petar and Dimković, Nada and Nedeljković, Ivana and Toljić, Boško and Vučinić, Nada",
year = "2013",
abstract = "Introduction. Paraoxonase 1 (PON1) is a multifunctional enzyme associated with high-density lipoprotein particles (HDL). It is a cellular antioxidant that hydrolyses oxidized macromolecules, especially low-density lipoproteins (ox-LDL). Because increased oxidative stress is believed to play a crucial role in the initiation and propagation of atherosclerosis, coding (Q192R and L55M) and promoter (C(-107)T) region polymorphisms of pon1 gene, that are responsible for catalytic efficiency, activity and the level of the enzyme, have been of great interest as a potential markers of susceptibility for atherogenesis. Objective. The aim of the study was to assess possible association between these pon1 gene variants and clinical manifestations of the atherosclerosis and oxidative stress. Methods. A total of 60 angiographically documented patients with manifested atherosclerotic disease and 100 control individuals were analyzed. Genomic DNA was isolated from the peripheral blood cells and genotyping was performed using polymerase chain reaction followed by the restriction fragment length polymorphism (PCR-RFLP) analysis. Results No significant difference in allele and genotype frequencies of all three examined polymorphisms was found between the atherosclerotic patients and healthy controls. The obtained results could not support an association of pon1 gene variants with the oxidative stress and atherogenesis. Conclusion. These polymorphisms cannot be considered risk factors of atherosclerosis in Serbian population. A larger study is required in order to establish possible contribution of pon1 variants to atherosclerosis-related cardiovascular diseases., Uvod. Paraoksonaza 1 (PON1) je multifunkcionalni enzim koji je vezan za lipoproteine visoke gustine (HDL). To je ćelijski antioksidans koji hidrolizuje oksidovane makromolekule, naročito oksidovane lipoproteine niske gustine (ox-LDL). Smatra se da povišeni oksidativni stres igra ključnu ulogu u inicijaciji i propagaciji ateroskleroze, pa su polimorfizmi u kodirajućem (Q192R i L55M) i promotorskom (C(-107)T) regionu gena pon1, koji su odgovorni za katalitičku efikasnost, aktivnost i nivo enzima, od velikog interesa kao potencijalni markeri osetljivosti na aterogenezu. Cilj rada. Cilj ove studije je bio da se ispita moguća povezanost varijanti gena pon1 i kliničkih manifestacija ateroskleroze i oksidativnog stresa. Metode rada. Analizirano je 60 bolesnika s angiografski dokumentovanim manifestacijama ateroskleroze i 100 zdravih ispitanika. Genomska DNK je izolovana iz ćelija periferne krvi, a genotipizacija je urađena primenom reakcije lančane polimeraze, posle koje je urađena analiza dužine restrikcionih fragmenata (tzv. PCR-RFLP analiza). Rezultati. Učestalosti alela i genotipova tri ispitivana polimorfizma nisu pokazale značajne razlike između ispitanika obolelih od ateroskleroze i zdravih osoba. Dobijeni rezultati ne ukazuju na povezanost analiziranih varijanti gena pon1 i oksidativnog stresa i aterogeneze. Zaključak. Ovi polimorfizmi se ne mogu smatrati faktorima rizika za razvoj ateroskleroze u srpskoj populaciji. Potrebna je studija sa većim brojem ispitanika, kako bi se utvrdio mogući doprinos varijanti gena pon1 na nastanak kardiovaskularnih oboljenja u čijoj osnovi je ateroskleroza.",
publisher = "Srpsko lekarsko društvo, Beograd",
journal = "Srpski arhiv za celokupno lekarstvo",
title = "Genetic polymorphisms of paraoxonase 1 and susceptibility to atherogenesis, Genetički polimorfizmi paraoksonaze 1 i podložnost aterogenezi",
volume = "141",
number = "9-10",
pages = "629-633",
doi = "10.2298/SARH1310629G"
}

Grubiša, I., Otašević, P., Dimković, N., Nedeljković, I., Toljić, B.,& Vučinić, N.. (2013). Genetic polymorphisms of paraoxonase 1 and susceptibility to atherogenesis. in Srpski arhiv za celokupno lekarstvo
Srpsko lekarsko društvo, Beograd., 141(9-10), 629-633.
https://doi.org/10.2298/SARH1310629G

Grubiša I, Otašević P, Dimković N, Nedeljković I, Toljić B, Vučinić N. Genetic polymorphisms of paraoxonase 1 and susceptibility to atherogenesis. in Srpski arhiv za celokupno lekarstvo. 2013;141(9-10):629-633.
doi:10.2298/SARH1310629G .

Grubiša, Ivana, Otašević, Petar, Dimković, Nada, Nedeljković, Ivana, Toljić, Boško, Vučinić, Nada, "Genetic polymorphisms of paraoxonase 1 and susceptibility to atherogenesis" in Srpski arhiv za celokupno lekarstvo, 141, no. 9-10 (2013):629-633,
https://doi.org/10.2298/SARH1310629G . .

TY  - JOUR
AU  - Grubiša, Ivana
AU  - Otašević, Petar
AU  - Despotović, Nebojša
AU  - Dedić, Velimir
AU  - Milašin, Jelena
AU  - Vučinić, Nada
PY  - 2013
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1807
AB  - One of the characteristics of type 2 diabetes mellitus (T2DM) is the state of persistent oxidative stress (OS) that has been implicated in the pathogenesis of diseases such is atherosclerosis mainly through chronic hyperglycemia that stimulates production of reactive oxygen species (ROS) and increases OS. Glutathione S-transferase P1 (GSTP1) is a member of the cytosolic GST superfamily. It plays an important role in neutralizing OS as an enzyme. Also, it participates in regulation of stress signaling and protects cells against apoptosis via its noncatalytic ligand-binding activity. GSTP1 Ile105Val functional polymorphism influences protein catalytic activity and stability and the aim of this study was to determine whether this gene variation influences susceptibility to atherogenesis in T2DM patients. A total of 240 individuals (140 patients with T2DM, accompanied with clinical manifestations of atherosclerosis, and 100 healthy controls) were included in this study. Genomic DNA was isolated from peripheral blood cells and genotyping was performed using polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) analysis. We obtained no statistically significant differences in the distribution of alleles and genotypes between cases and controls (P>0.05) but association between Ile/Val (OR=0.6, 95%CI=0.35-1.05, P=0.08) and Val/Val (OR=0.45, 95%CI=0.18-1.11, P=0.08) genotypes and disease approached significance (P=0.08). Our results indicated that a larger study group is needed to establish the true relationship between potentialiy protective allele Val and the disease, and to determine the influence of other GSTP1 polymorphisms on atherogenesis in T2DM patients.
AB  - Jedna od osobina tipa 2 dijabetes mellitus (T2DM) je stanje perzistentnog oksidativnog stresa (OS) koji je sastavni deo patogeneze bolesti kao što je ateroskleroza i to najčešće putem hronične hiperglikemije koja stimuliše nastanak reaktivnih vrsta kiseonika (tzv ROS) i povećava nivo OS. Glutation S-transferaza P1 (GSTP1) pripada superfamiliji citosolnih GST. Kao enzim, ima važnu ulogu u neutralizaciji OS. Takođe, učestvuje u regulaciji signalnog puta stresa ali i štiti ćelije od apoptoze putem nekatalitičke ligand-vezujuće aktivnosti. Funkcionalni polimorfizam Ile105Val GSTP1 gena utiče na katalitičku aktivnost proteina i na njegovu stabilnost i cilj ove studije je bio da se utvrdi da li ova genska varijanta utiče na osetljivost na aterogenezu kod pacijenata sa T2DM. Ukupno 240 osobe (140 pacijenata sa T2DM i nekom od kliničkih manifestacija ateroskleroze i 100 zdravih kontrola) je bilo uključeno u ovu studiju. Genomska DNK je izolovana iz ćelija periferne krvi a genotipizacija je urađena primenom reakcije lančane polimeraze posle koje je urađena analiza dužine restrikcionih fragmenata (PCR-RFLP analiza). Nismo dobili statistički značajne razlike u raspodeli alela i genotipova između obolelih i kontrola (P>0.05) ali asocijacija između Ile/Val (OR=0.6, 95%CI=0.35-1.05, P=0.08) i Val/Val (OR=0.45, 95%CI=0.18-1.11, P=0.08) genotipova i bolesti se približila značajnosti (P=0.08). Naši rezultaati pokazuju da je potrebna veća grupa ispitanika da bi se utvrdila prava veza između potencijalno protektivnog alela Val i bolesti kao i da bi se utvrdio uticaj drugih polimorfizama gena GSTP1 na aterogenezu kod T2DM pacijenata.
PB  - Društvo genetičara Srbije, Beograd
T2  - Genetika
T1  - Genetic polymorphism of glutathion S-transferase P1 (GSTP1) Ile105Val and susceptibility to atherogenesis in patients with type 2 diabetes mellitus
T1  - Genetički polimorfizam glutation S-transferaze P1 (GSTP1) Ile105Val i osetljivost na aterogenezu kod pacijenata sa dijabetesom tipa 2
VL  - 45
IS  - 1
SP  - 227
EP  - 236
DO  - 10.2298/GENSR1301227G
ER  - 

@article{
author = "Grubiša, Ivana and Otašević, Petar and Despotović, Nebojša and Dedić, Velimir and Milašin, Jelena and Vučinić, Nada",
year = "2013",
abstract = "One of the characteristics of type 2 diabetes mellitus (T2DM) is the state of persistent oxidative stress (OS) that has been implicated in the pathogenesis of diseases such is atherosclerosis mainly through chronic hyperglycemia that stimulates production of reactive oxygen species (ROS) and increases OS. Glutathione S-transferase P1 (GSTP1) is a member of the cytosolic GST superfamily. It plays an important role in neutralizing OS as an enzyme. Also, it participates in regulation of stress signaling and protects cells against apoptosis via its noncatalytic ligand-binding activity. GSTP1 Ile105Val functional polymorphism influences protein catalytic activity and stability and the aim of this study was to determine whether this gene variation influences susceptibility to atherogenesis in T2DM patients. A total of 240 individuals (140 patients with T2DM, accompanied with clinical manifestations of atherosclerosis, and 100 healthy controls) were included in this study. Genomic DNA was isolated from peripheral blood cells and genotyping was performed using polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) analysis. We obtained no statistically significant differences in the distribution of alleles and genotypes between cases and controls (P>0.05) but association between Ile/Val (OR=0.6, 95%CI=0.35-1.05, P=0.08) and Val/Val (OR=0.45, 95%CI=0.18-1.11, P=0.08) genotypes and disease approached significance (P=0.08). Our results indicated that a larger study group is needed to establish the true relationship between potentialiy protective allele Val and the disease, and to determine the influence of other GSTP1 polymorphisms on atherogenesis in T2DM patients., Jedna od osobina tipa 2 dijabetes mellitus (T2DM) je stanje perzistentnog oksidativnog stresa (OS) koji je sastavni deo patogeneze bolesti kao što je ateroskleroza i to najčešće putem hronične hiperglikemije koja stimuliše nastanak reaktivnih vrsta kiseonika (tzv ROS) i povećava nivo OS. Glutation S-transferaza P1 (GSTP1) pripada superfamiliji citosolnih GST. Kao enzim, ima važnu ulogu u neutralizaciji OS. Takođe, učestvuje u regulaciji signalnog puta stresa ali i štiti ćelije od apoptoze putem nekatalitičke ligand-vezujuće aktivnosti. Funkcionalni polimorfizam Ile105Val GSTP1 gena utiče na katalitičku aktivnost proteina i na njegovu stabilnost i cilj ove studije je bio da se utvrdi da li ova genska varijanta utiče na osetljivost na aterogenezu kod pacijenata sa T2DM. Ukupno 240 osobe (140 pacijenata sa T2DM i nekom od kliničkih manifestacija ateroskleroze i 100 zdravih kontrola) je bilo uključeno u ovu studiju. Genomska DNK je izolovana iz ćelija periferne krvi a genotipizacija je urađena primenom reakcije lančane polimeraze posle koje je urađena analiza dužine restrikcionih fragmenata (PCR-RFLP analiza). Nismo dobili statistički značajne razlike u raspodeli alela i genotipova između obolelih i kontrola (P>0.05) ali asocijacija između Ile/Val (OR=0.6, 95%CI=0.35-1.05, P=0.08) i Val/Val (OR=0.45, 95%CI=0.18-1.11, P=0.08) genotipova i bolesti se približila značajnosti (P=0.08). Naši rezultaati pokazuju da je potrebna veća grupa ispitanika da bi se utvrdila prava veza između potencijalno protektivnog alela Val i bolesti kao i da bi se utvrdio uticaj drugih polimorfizama gena GSTP1 na aterogenezu kod T2DM pacijenata.",
publisher = "Društvo genetičara Srbije, Beograd",
journal = "Genetika",
title = "Genetic polymorphism of glutathion S-transferase P1 (GSTP1) Ile105Val and susceptibility to atherogenesis in patients with type 2 diabetes mellitus, Genetički polimorfizam glutation S-transferaze P1 (GSTP1) Ile105Val i osetljivost na aterogenezu kod pacijenata sa dijabetesom tipa 2",
volume = "45",
number = "1",
pages = "227-236",
doi = "10.2298/GENSR1301227G"
}

Grubiša, I., Otašević, P., Despotović, N., Dedić, V., Milašin, J.,& Vučinić, N.. (2013). Genetic polymorphism of glutathion S-transferase P1 (GSTP1) Ile105Val and susceptibility to atherogenesis in patients with type 2 diabetes mellitus. in Genetika
Društvo genetičara Srbije, Beograd., 45(1), 227-236.
https://doi.org/10.2298/GENSR1301227G

Grubiša I, Otašević P, Despotović N, Dedić V, Milašin J, Vučinić N. Genetic polymorphism of glutathion S-transferase P1 (GSTP1) Ile105Val and susceptibility to atherogenesis in patients with type 2 diabetes mellitus. in Genetika. 2013;45(1):227-236.
doi:10.2298/GENSR1301227G .

Grubiša, Ivana, Otašević, Petar, Despotović, Nebojša, Dedić, Velimir, Milašin, Jelena, Vučinić, Nada, "Genetic polymorphism of glutathion S-transferase P1 (GSTP1) Ile105Val and susceptibility to atherogenesis in patients with type 2 diabetes mellitus" in Genetika, 45, no. 1 (2013):227-236,
https://doi.org/10.2298/GENSR1301227G . .