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 . .