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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
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
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URI
http://smile.stomf.bg.ac.rs/handle/123456789/2526
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Stomatološki fakultet

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