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Current Drug Metabolism

Editor-in-Chief

ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

Review Article

Pharmacogenomics of Methotrexate: Current Status and Future Outlook

Author(s): Mengda Cao, Miao Guo, De-Qin Wu* and Ling Meng*

Volume 19 , Issue 14 , 2018

Page: [1182 - 1187] Pages: 6

DOI: 10.2174/1389200219666171227201047

Price: $65

Sekisui-XenoTech-CDM
Abstract

Background: Methotrexate (MTX) is a folate analogue with high therapeutic efficiency in the treatment of cancers and autoimmune diseases. The efficacy and toxicity of MTX may be altered by genetic polymorphisms in genes involved in MTX metabolic pathway. Personalized pharmacotherapy based on gene polymorphisms enables a more efficient, compatible and cost-effective treatment of patients.

Objective: The present article aims to review genetic polymorphisms associated with MTX pharmacokinetics, toxicity, and outcome, and points out future development directions of individualized MTX therapy.

Methods: Details regarding the pharmacogenetics and pharmacogenomics of MTX are obtained from PubMed literatures.

Conclusion: The influences of single nucleotide polymorphisms (SNPs) in genes involved in MTX pathway are controversial. Many pharmacogenetic associations are disease specific and race specific. Present studies have almost limited to some certain ethnic groups and diseases. The data from these studies are not convincing enough to draw far-reaching conclusions about the applicability of MTX pharmacogenetics in clinical practice. Studies with large scale and multiple centers are needed in the future. MTX-PG inhibits folic metabolism through three mechanisms. TS, MTHFR and ATIC are the rate-limiting enzymes separately. The function of SNPs in these genes is often onesided. Works focusing on the analysis of polymorphism in MTX transporters should be more efficient and meaningful.

Keywords: MTX, SNP, efficacy, toxicity, pharmacogenomics, polymorphisms.

Graphical Abstract

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