TY  - JOUR
AU  - Vejnović, Dubravka
AU  - Milić, Vera
AU  - Popović, Branka
AU  - Damnjanović, Tatjana
AU  - Maksimović, Nela
AU  - Bunjevački, Vera
AU  - Krajinović, Maja
AU  - Novaković, Ivana
AU  - Damjanov, Nemanja
AU  - Jekić, Biljana
PY  - 2019
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/2526
AB  - Background: Methotrexate (MTX), a folate analogue, is the most commonly used disease-modifying drug in the treatment of rheumatoid arthritis (RA). However, high interindividual differences in drug response are present among RA patients.Research design and methods: In a group of 234 RA patients treated with MTX, we investigated whether rs1650697 polymorphism in DHFR gene may have an impact on MTX efficacy and/or adverse drug effects (ADEs). Relative DAS28 values (rDAS28) were used for the estimation of MTX therapy and all ADEs were recorded. Patients were genotyped for selected polymorphism by real-time PCR method. Results: According to the European League Against Rheumatism criteria after 6 months of MTX therapy, 196 patients (83.8%) were classified as responders (25 (10.7%) were good and 171 (73.1%) were moderate) and 38 patients (16.2%) as nonresponders. ADEs were observed in 55 patients (23.5%). Conclusions: Our results showed that the presence of T allele might be protective against MTX hepatotoxicity measured by transaminase levels (p = 0.05). Furthermore, among patients who also received low-dose corticosteroids, we have found a lower rDAS value in patients with CC genotype (p = 0.039).
PB  - Taylor & Francis Ltd, Abingdon
T2  - Expert Opinion on Drug Metabolism & Toxicology
T1  - Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients
VL  - 15
IS  - 3
SP  - 253
EP  - 257
DO  - 10.1080/17425255.2019.1563594
ER  - 

@article{
author = "Vejnović, Dubravka and Milić, Vera and Popović, Branka and Damnjanović, Tatjana and Maksimović, Nela and Bunjevački, Vera and Krajinović, Maja and Novaković, Ivana and Damjanov, Nemanja and Jekić, Biljana",
year = "2019",
abstract = "Background: Methotrexate (MTX), a folate analogue, is the most commonly used disease-modifying drug in the treatment of rheumatoid arthritis (RA). However, high interindividual differences in drug response are present among RA patients.Research design and methods: In a group of 234 RA patients treated with MTX, we investigated whether rs1650697 polymorphism in DHFR gene may have an impact on MTX efficacy and/or adverse drug effects (ADEs). Relative DAS28 values (rDAS28) were used for the estimation of MTX therapy and all ADEs were recorded. Patients were genotyped for selected polymorphism by real-time PCR method. Results: According to the European League Against Rheumatism criteria after 6 months of MTX therapy, 196 patients (83.8%) were classified as responders (25 (10.7%) were good and 171 (73.1%) were moderate) and 38 patients (16.2%) as nonresponders. ADEs were observed in 55 patients (23.5%). Conclusions: Our results showed that the presence of T allele might be protective against MTX hepatotoxicity measured by transaminase levels (p = 0.05). Furthermore, among patients who also received low-dose corticosteroids, we have found a lower rDAS value in patients with CC genotype (p = 0.039).",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Expert Opinion on Drug Metabolism & Toxicology",
title = "Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients",
volume = "15",
number = "3",
pages = "253-257",
doi = "10.1080/17425255.2019.1563594"
}

Vejnović, D., Milić, V., Popović, B., Damnjanović, T., Maksimović, N., Bunjevački, V., Krajinović, M., Novaković, I., Damjanov, N.,& Jekić, B.. (2019). Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients. in Expert Opinion on Drug Metabolism & Toxicology
Taylor & Francis Ltd, Abingdon., 15(3), 253-257.
https://doi.org/10.1080/17425255.2019.1563594

Vejnović D, Milić V, Popović B, Damnjanović T, Maksimović N, Bunjevački V, Krajinović M, Novaković I, Damjanov N, Jekić B. Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients. in Expert Opinion on Drug Metabolism & Toxicology. 2019;15(3):253-257.
doi:10.1080/17425255.2019.1563594 .

Vejnović, Dubravka, Milić, Vera, Popović, Branka, Damnjanović, Tatjana, Maksimović, Nela, Bunjevački, Vera, Krajinović, Maja, Novaković, Ivana, Damjanov, Nemanja, Jekić, Biljana, "Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients" in Expert Opinion on Drug Metabolism & Toxicology, 15, no. 3 (2019):253-257,
https://doi.org/10.1080/17425255.2019.1563594 . .

TY  - JOUR
AU  - Vejnović, Dubravka
AU  - Milić, Vera
AU  - Popović, Branka
AU  - Damnjanović, Tatjana
AU  - Maksimović, Nela
AU  - Bunjevački, Vera
AU  - Krajinović, Maja
AU  - Novaković, Ivana
AU  - Damjanov, Nemanja
AU  - Jekić, Biljana
PY  - 2019
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/2462
AB  - Background: Methotrexate (MTX), a folate analogue, is the most commonly used disease-modifying drug in the treatment of rheumatoid arthritis (RA). However, high interindividual differences in drug response are present among RA patients.Research design and methods: In a group of 234 RA patients treated with MTX, we investigated whether rs1650697 polymorphism in DHFR gene may have an impact on MTX efficacy and/or adverse drug effects (ADEs). Relative DAS28 values (rDAS28) were used for the estimation of MTX therapy and all ADEs were recorded. Patients were genotyped for selected polymorphism by real-time PCR method. Results: According to the European League Against Rheumatism criteria after 6 months of MTX therapy, 196 patients (83.8%) were classified as responders (25 (10.7%) were good and 171 (73.1%) were moderate) and 38 patients (16.2%) as nonresponders. ADEs were observed in 55 patients (23.5%). Conclusions: Our results showed that the presence of T allele might be protective against MTX hepatotoxicity measured by transaminase levels (p = 0.05). Furthermore, among patients who also received low-dose corticosteroids, we have found a lower rDAS value in patients with CC genotype (p = 0.039).
PB  - Taylor & Francis Ltd, Abingdon
T2  - Expert Opinion on Drug Metabolism & Toxicology
T1  - Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients
VL  - 15
IS  - 3
SP  - 253
EP  - 257
DO  - 10.1080/17425255.2019.1563594
ER  - 

@article{
author = "Vejnović, Dubravka and Milić, Vera and Popović, Branka and Damnjanović, Tatjana and Maksimović, Nela and Bunjevački, Vera and Krajinović, Maja and Novaković, Ivana and Damjanov, Nemanja and Jekić, Biljana",
year = "2019",
abstract = "Background: Methotrexate (MTX), a folate analogue, is the most commonly used disease-modifying drug in the treatment of rheumatoid arthritis (RA). However, high interindividual differences in drug response are present among RA patients.Research design and methods: In a group of 234 RA patients treated with MTX, we investigated whether rs1650697 polymorphism in DHFR gene may have an impact on MTX efficacy and/or adverse drug effects (ADEs). Relative DAS28 values (rDAS28) were used for the estimation of MTX therapy and all ADEs were recorded. Patients were genotyped for selected polymorphism by real-time PCR method. Results: According to the European League Against Rheumatism criteria after 6 months of MTX therapy, 196 patients (83.8%) were classified as responders (25 (10.7%) were good and 171 (73.1%) were moderate) and 38 patients (16.2%) as nonresponders. ADEs were observed in 55 patients (23.5%). Conclusions: Our results showed that the presence of T allele might be protective against MTX hepatotoxicity measured by transaminase levels (p = 0.05). Furthermore, among patients who also received low-dose corticosteroids, we have found a lower rDAS value in patients with CC genotype (p = 0.039).",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Expert Opinion on Drug Metabolism & Toxicology",
title = "Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients",
volume = "15",
number = "3",
pages = "253-257",
doi = "10.1080/17425255.2019.1563594"
}

Vejnović, D., Milić, V., Popović, B., Damnjanović, T., Maksimović, N., Bunjevački, V., Krajinović, M., Novaković, I., Damjanov, N.,& Jekić, B.. (2019). Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients. in Expert Opinion on Drug Metabolism & Toxicology
Taylor & Francis Ltd, Abingdon., 15(3), 253-257.
https://doi.org/10.1080/17425255.2019.1563594

Vejnović D, Milić V, Popović B, Damnjanović T, Maksimović N, Bunjevački V, Krajinović M, Novaković I, Damjanov N, Jekić B. Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients. in Expert Opinion on Drug Metabolism & Toxicology. 2019;15(3):253-257.
doi:10.1080/17425255.2019.1563594 .

Vejnović, Dubravka, Milić, Vera, Popović, Branka, Damnjanović, Tatjana, Maksimović, Nela, Bunjevački, Vera, Krajinović, Maja, Novaković, Ivana, Damjanov, Nemanja, Jekić, Biljana, "Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients" in Expert Opinion on Drug Metabolism & Toxicology, 15, no. 3 (2019):253-257,
https://doi.org/10.1080/17425255.2019.1563594 . .

TY  - JOUR
AU  - Jekić, Biljana
AU  - Luković, Ljiljana
AU  - Bunjevački, Vera
AU  - Milić, Vera
AU  - Novaković, Ivana
AU  - Damnjanović, Tatjana
AU  - Milašin, Jelena
AU  - Popović, Branka
AU  - Maksimović, Nela
AU  - Damjanov, Nemanja
AU  - Radunović, Goran
AU  - Kovacević, Ljiljana
AU  - Krajinović, Maja
PY  - 2013
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1839
AB  - Purpose Gamma-glutamyl hydrolase (GGH), cyclin D1 (CCND1) and thymidylate synthase (TS) genes encode enzymes that are involved in methotrexate (MTX) action. In a group of 184 RA patients treated with MTX, we have investigated whether selected polymorphisms in these genes modulate MTX efficacy and/or have impact on adverse drug effects (ADEs). Methods The efficacy of the MTX therapy has been estimated using the disease activity score in 28 joints (DAS28-ESR) based on EULAR criteria and relative DAS28 values (rDAS28). All adverse drug events were recorded. Patients were genotyped for selected polymorphisms of the GGH (-354 G>T and 452 C>T), CCND1 (870 A>G) and TYMS (variable number of tandem repeats, VNTR, and G to C substitution of triple repeat, 3R allele) gene. Association studies have been performed between obtained genotypes and the efficacy and toxicity of MTX. Results According to the EULAR response criteria, 146 RA patients (79.3 %) were classified as responders (good/moderate response) and 38 (20.7 %) as nonresponders (poor response). Higher frequency of the TYMS 3 G/3 G genotype has been found among non-responders as compared to individuals with remaining genotypes (p=0.02). ADEs were recorded in 53 patients. Among those patients eight experienced bone marrow toxicity, all of them carried GGH -354GG genotype (p=0.003). No other significant association were observed. Conclusion The 3 G/3 G genotype of the TYMS gene may indicate predisposition of poor response to MTX and GG genotype of GGH -354 T>G polymorphism may have high predictive value for myelosuppression in RA patients.
PB  - Springer Heidelberg, Heidelberg
T2  - European Journal of Clinical Pharmacology
T1  - Association of the TYMS 3G/3G genotype with poor response and GGH 354GG genotype with the bone marrow toxicity of the methotrexate in RA patients
VL  - 69
IS  - 3
SP  - 377
EP  - 383
DO  - 10.1007/s00228-012-1341-3
ER  - 

@article{
author = "Jekić, Biljana and Luković, Ljiljana and Bunjevački, Vera and Milić, Vera and Novaković, Ivana and Damnjanović, Tatjana and Milašin, Jelena and Popović, Branka and Maksimović, Nela and Damjanov, Nemanja and Radunović, Goran and Kovacević, Ljiljana and Krajinović, Maja",
year = "2013",
abstract = "Purpose Gamma-glutamyl hydrolase (GGH), cyclin D1 (CCND1) and thymidylate synthase (TS) genes encode enzymes that are involved in methotrexate (MTX) action. In a group of 184 RA patients treated with MTX, we have investigated whether selected polymorphisms in these genes modulate MTX efficacy and/or have impact on adverse drug effects (ADEs). Methods The efficacy of the MTX therapy has been estimated using the disease activity score in 28 joints (DAS28-ESR) based on EULAR criteria and relative DAS28 values (rDAS28). All adverse drug events were recorded. Patients were genotyped for selected polymorphisms of the GGH (-354 G>T and 452 C>T), CCND1 (870 A>G) and TYMS (variable number of tandem repeats, VNTR, and G to C substitution of triple repeat, 3R allele) gene. Association studies have been performed between obtained genotypes and the efficacy and toxicity of MTX. Results According to the EULAR response criteria, 146 RA patients (79.3 %) were classified as responders (good/moderate response) and 38 (20.7 %) as nonresponders (poor response). Higher frequency of the TYMS 3 G/3 G genotype has been found among non-responders as compared to individuals with remaining genotypes (p=0.02). ADEs were recorded in 53 patients. Among those patients eight experienced bone marrow toxicity, all of them carried GGH -354GG genotype (p=0.003). No other significant association were observed. Conclusion The 3 G/3 G genotype of the TYMS gene may indicate predisposition of poor response to MTX and GG genotype of GGH -354 T>G polymorphism may have high predictive value for myelosuppression in RA patients.",
publisher = "Springer Heidelberg, Heidelberg",
journal = "European Journal of Clinical Pharmacology",
title = "Association of the TYMS 3G/3G genotype with poor response and GGH 354GG genotype with the bone marrow toxicity of the methotrexate in RA patients",
volume = "69",
number = "3",
pages = "377-383",
doi = "10.1007/s00228-012-1341-3"
}

Jekić, B., Luković, L., Bunjevački, V., Milić, V., Novaković, I., Damnjanović, T., Milašin, J., Popović, B., Maksimović, N., Damjanov, N., Radunović, G., Kovacević, L.,& Krajinović, M.. (2013). Association of the TYMS 3G/3G genotype with poor response and GGH 354GG genotype with the bone marrow toxicity of the methotrexate in RA patients. in European Journal of Clinical Pharmacology
Springer Heidelberg, Heidelberg., 69(3), 377-383.
https://doi.org/10.1007/s00228-012-1341-3

Jekić B, Luković L, Bunjevački V, Milić V, Novaković I, Damnjanović T, Milašin J, Popović B, Maksimović N, Damjanov N, Radunović G, Kovacević L, Krajinović M. Association of the TYMS 3G/3G genotype with poor response and GGH 354GG genotype with the bone marrow toxicity of the methotrexate in RA patients. in European Journal of Clinical Pharmacology. 2013;69(3):377-383.
doi:10.1007/s00228-012-1341-3 .

Jekić, Biljana, Luković, Ljiljana, Bunjevački, Vera, Milić, Vera, Novaković, Ivana, Damnjanović, Tatjana, Milašin, Jelena, Popović, Branka, Maksimović, Nela, Damjanov, Nemanja, Radunović, Goran, Kovacević, Ljiljana, Krajinović, Maja, "Association of the TYMS 3G/3G genotype with poor response and GGH 354GG genotype with the bone marrow toxicity of the methotrexate in RA patients" in European Journal of Clinical Pharmacology, 69, no. 3 (2013):377-383,
https://doi.org/10.1007/s00228-012-1341-3 . .

TY  - JOUR
AU  - Milić, Vera
AU  - Jekić, Biljana
AU  - Luković, Ljiljana
AU  - Bunjevački, Vera
AU  - Milašin, Jelena
AU  - Novaković, I.
AU  - Damnjanović, Tatjana
AU  - Popović, Branka
AU  - Maksimović, Nela
AU  - Damjanov, Nemanja
AU  - Radunović, Goran
AU  - Pejnović, Nada
AU  - Krajinović, Maja
PY  - 2012
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1741
AB  - Objectives Identifying genetic predictors of methotrexate (MTX) treatment response in patients with rheumatoid arthritis (RA) may have great importance for optimising drug doses required for clinical benefit without toxicity. In a group of 125 RA patients treated with MTX we investigated whether selected polymorphisms in genes relevant for MTX action (aminoimidazole-4-carboxiamide ribonucleotide transformylase, ATIC, and dihydrofolate reductase, DHFR) modulate disease activity and/or have impact on therapy side effects. Methods The efficacy of treatment was estimated both by the disease activity score in 28 joints (DAS28), based on EULAR criteria, and relative DAS28 (rDAS28) score. Adverse drug events (ADEs) were also recorded. RA patients were genotyped using the PCR-RFLP method, followed by an association study between ATIC -129T>G, DHFR -216T>C and DHFR -317A>G polymorphisms and the efficacy and toxicity of MTX. Results According to the EULAR response criteria, 96 RA patients (76.8%) were classified as responders (good/moderate response) and 29 (23.2%) as non-responders (poor response). rDAS28 values ranged from -0.01 to 0.80 (mean value 0.31 +/- 0.19). Among 125 patients enrolled in this study 39 experienced at least one side effect. The DHFR -317AA genotype was associated with the less favourable response (reduction in rDAS28 score, p=0.05). None of the analysed polymorphisms was associated with MTX toxicity. Conclusion RA patients with DHFR-317AA genotype had less favourable response to MTX Further studies in larger patient populations are necessary to confirm the relationship between the analysed polymorphisms and MTX treatment response.
PB  - Clinical & Exper Rheumatology, Pisa
T2  - Clinical & Experimental Rheumatology
T1  - Association of dihydrofolate reductase (DHFR)-317AA genotype with poor response to methotrexate in patients with rheumatoid arthritis
VL  - 30
IS  - 2
SP  - 178
EP  - 183
UR  - https://hdl.handle.net/21.15107/rcub_smile_1741
ER  - 

@article{
author = "Milić, Vera and Jekić, Biljana and Luković, Ljiljana and Bunjevački, Vera and Milašin, Jelena and Novaković, I. and Damnjanović, Tatjana and Popović, Branka and Maksimović, Nela and Damjanov, Nemanja and Radunović, Goran and Pejnović, Nada and Krajinović, Maja",
year = "2012",
abstract = "Objectives Identifying genetic predictors of methotrexate (MTX) treatment response in patients with rheumatoid arthritis (RA) may have great importance for optimising drug doses required for clinical benefit without toxicity. In a group of 125 RA patients treated with MTX we investigated whether selected polymorphisms in genes relevant for MTX action (aminoimidazole-4-carboxiamide ribonucleotide transformylase, ATIC, and dihydrofolate reductase, DHFR) modulate disease activity and/or have impact on therapy side effects. Methods The efficacy of treatment was estimated both by the disease activity score in 28 joints (DAS28), based on EULAR criteria, and relative DAS28 (rDAS28) score. Adverse drug events (ADEs) were also recorded. RA patients were genotyped using the PCR-RFLP method, followed by an association study between ATIC -129T>G, DHFR -216T>C and DHFR -317A>G polymorphisms and the efficacy and toxicity of MTX. Results According to the EULAR response criteria, 96 RA patients (76.8%) were classified as responders (good/moderate response) and 29 (23.2%) as non-responders (poor response). rDAS28 values ranged from -0.01 to 0.80 (mean value 0.31 +/- 0.19). Among 125 patients enrolled in this study 39 experienced at least one side effect. The DHFR -317AA genotype was associated with the less favourable response (reduction in rDAS28 score, p=0.05). None of the analysed polymorphisms was associated with MTX toxicity. Conclusion RA patients with DHFR-317AA genotype had less favourable response to MTX Further studies in larger patient populations are necessary to confirm the relationship between the analysed polymorphisms and MTX treatment response.",
publisher = "Clinical & Exper Rheumatology, Pisa",
journal = "Clinical & Experimental Rheumatology",
title = "Association of dihydrofolate reductase (DHFR)-317AA genotype with poor response to methotrexate in patients with rheumatoid arthritis",
volume = "30",
number = "2",
pages = "178-183",
url = "https://hdl.handle.net/21.15107/rcub_smile_1741"
}

Milić, V., Jekić, B., Luković, L., Bunjevački, V., Milašin, J., Novaković, I., Damnjanović, T., Popović, B., Maksimović, N., Damjanov, N., Radunović, G., Pejnović, N.,& Krajinović, M.. (2012). Association of dihydrofolate reductase (DHFR)-317AA genotype with poor response to methotrexate in patients with rheumatoid arthritis. in Clinical & Experimental Rheumatology
Clinical & Exper Rheumatology, Pisa., 30(2), 178-183.
https://hdl.handle.net/21.15107/rcub_smile_1741

Milić V, Jekić B, Luković L, Bunjevački V, Milašin J, Novaković I, Damnjanović T, Popović B, Maksimović N, Damjanov N, Radunović G, Pejnović N, Krajinović M. Association of dihydrofolate reductase (DHFR)-317AA genotype with poor response to methotrexate in patients with rheumatoid arthritis. in Clinical & Experimental Rheumatology. 2012;30(2):178-183.
https://hdl.handle.net/21.15107/rcub_smile_1741 .

Milić, Vera, Jekić, Biljana, Luković, Ljiljana, Bunjevački, Vera, Milašin, Jelena, Novaković, I., Damnjanović, Tatjana, Popović, Branka, Maksimović, Nela, Damjanov, Nemanja, Radunović, Goran, Pejnović, Nada, Krajinović, Maja, "Association of dihydrofolate reductase (DHFR)-317AA genotype with poor response to methotrexate in patients with rheumatoid arthritis" in Clinical & Experimental Rheumatology, 30, no. 2 (2012):178-183,
https://hdl.handle.net/21.15107/rcub_smile_1741 .