Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients
Аутори
Vejnović, DubravkaMilić, Vera
Popović, Branka
Damnjanović, Tatjana
Maksimović, Nela
Bunjevački, Vera
Krajinović, Maja
Novaković, Ivana
Damjanov, Nemanja
Jekić, Biljana
Чланак у часопису (Рецензирана верзија)
Метаподаци
Приказ свих података о документуАпстракт
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 agains...t 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).
Кључне речи:
DHFR / genetic polymorphism / methotrexate / pharmacogenetics / rheumatoid arthritis / toxicityИзвор:
Expert Opinion on Drug Metabolism & Toxicology, 2019, 15, 3, 253-257Издавач:
- Taylor & Francis Ltd, Abingdon
Финансирање / пројекти:
- Анализа генетичких маркера мишићне дистоније (RS-MESTD-Basic Research (BR or ON)-175091)
Напомена:
- This is the peer-reviewed version of the article: 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. Expert Opinion on Drug Metabolism & Toxicology 2019, 15 (3), 253–257. https://doi.org/10.1080/17425255.2019.1563594
DOI: 10.1080/17425255.2019.1563594
ISSN: 1742-5255
PubMed: 30583708
WoS: 000458880400007
Scopus: 2-s2.0-85059575374
Колекције
Институција/група
Stomatološki fakultetTY - 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 . .