Genetic markers in methotrexate treatments
- PMID: 30237581
- DOI: 10.1038/s41397-018-0047-z
Genetic markers in methotrexate treatments
Abstract
Methotrexate (MTX), a structural analog of folic acid, is widely employed in the treatment of different cancers and autoimmune diseases. Despite the successful results observed, the main disadvantage lies in interpatient variability in the pharmacokinetic and pharmacodynamic parameters. In particular, adverse events and toxicities induced by MTX are a matter of concern and can be the cause of dose reduction or treatment discontinuation. Among the different approaches to reduce MTX therapeutic limitations, pharmacogenomics contributes by considering the effect of inherited genetic differences on those parameters. This review provides an update on MTX pharmacogenomics. It reports the contribution of main gene polymorphisms involved in the influx, efflux, cellular effect, and elimination on MTX toxicity and efficacy, on all the diseases treated with this drug. From the analysis of the data presented in this review, we concluded that only gene polymorphisms MTHFR rs1801133, SLC19A1 rs1051266, and TYMS rs34743033 could influence clinical decision-making.
Similar articles
-
Germline genetic variations in methotrexate candidate genes are associated with pharmacokinetics, toxicity, and outcome in childhood acute lymphoblastic leukemia.Blood. 2013 Jun 27;121(26):5145-53. doi: 10.1182/blood-2013-01-480335. Epub 2013 May 7. Blood. 2013. PMID: 23652803
-
Association of genetic polymorphism in the folate metabolic pathway with methotrexate pharmacokinetics and toxicity in childhood acute lymphoblastic leukaemia and malignant lymphoma.Eur J Clin Pharmacol. 2011 Oct;67(10):993-1006. doi: 10.1007/s00228-011-1046-z. Epub 2011 Apr 21. Eur J Clin Pharmacol. 2011. PMID: 21509569
-
Methotrexate pharmacogenetics in Uruguayan adults with hematological malignant diseases.Eur J Pharm Sci. 2017 Nov 15;109:480-485. doi: 10.1016/j.ejps.2017.09.006. Epub 2017 Sep 5. Eur J Pharm Sci. 2017. PMID: 28887233 Clinical Trial.
-
Pharmacogenomics of Methotrexate: Current Status and Future Outlook.Curr Drug Metab. 2018;19(14):1182-1187. doi: 10.2174/1389200219666171227201047. Curr Drug Metab. 2018. PMID: 29283070 Review.
-
Methotrexate-induced toxicity pharmacogenetics: an umbrella review of systematic reviews and meta-analyses.Cancer Chemother Pharmacol. 2016 Jul;78(1):27-39. doi: 10.1007/s00280-016-3043-5. Epub 2016 May 3. Cancer Chemother Pharmacol. 2016. PMID: 27142726
Cited by
-
In Silico Study Probes Potential Inhibitors of Human Dihydrofolate Reductase for Cancer Therapeutics.J Clin Med. 2019 Feb 11;8(2):233. doi: 10.3390/jcm8020233. J Clin Med. 2019. PMID: 30754680 Free PMC article.
-
Contribution of genetic polymorphism of methylene tetrahydrofolate reductase on the effect of methotrexate in ectopic pregnancy patients.J Clin Lab Anal. 2020 Jan;34(1):e23030. doi: 10.1002/jcla.23030. Epub 2019 Sep 10. J Clin Lab Anal. 2020. PMID: 31502727 Free PMC article.
-
Unveiling the Efficacy of Sesquiterpenes from Marine Sponge Dactylospongia elegans in Inhibiting Dihydrofolate Reductase Using Docking and Molecular Dynamic Studies.Molecules. 2023 Jan 29;28(3):1292. doi: 10.3390/molecules28031292. Molecules. 2023. PMID: 36770958 Free PMC article.
-
Pharmacogenomics on the Treatment Response in Patients with Psoriasis: An Updated Review.Int J Mol Sci. 2023 Apr 15;24(8):7329. doi: 10.3390/ijms24087329. Int J Mol Sci. 2023. PMID: 37108492 Free PMC article. Review.
-
Association between high-dose methotrexate-induced toxicity and polymorphisms within methotrexate pathway genes in acute lymphoblastic leukemia.Front Pharmacol. 2022 Nov 30;13:1003812. doi: 10.3389/fphar.2022.1003812. eCollection 2022. Front Pharmacol. 2022. PMID: 36532750 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources