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Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients

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2019
Association_of_C35T_acc_2019.pdf (919.6Kb)
Authors
Vejnović, Dubravka
Milić, Vera
Popović, Branka
Damnjanović, Tatjana
Maksimović, Nela
Bunjevački, Vera
Krajinović, Maja
Novaković, Ivana
Damjanov, Nemanja
Jekić, Biljana
Article (Accepted Version)
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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 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).

Keywords:
DHFR / genetic polymorphism / methotrexate / pharmacogenetics / rheumatoid arthritis / toxicity
Source:
Expert Opinion on Drug Metabolism & Toxicology, 2019, 15, 3, 253-257
Publisher:
  • Taylor & Francis Ltd, Abingdon
Funding / projects:
  • The Analysis of Genetic Markers of Muscle Dystonia (RS-175091)
Note:
  • 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
[ Google Scholar ]
3
3
URI
https://smile.stomf.bg.ac.rs/handle/123456789/2526
Collections
  • Radovi istraživača
Institution/Community
Stomatološki fakultet
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 . .

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