Title:Pharmacogenomics of Methotrexate: Current Status and Future Outlook
Volume: 19
Issue: 14
Author(s): Mengda Cao, Miao Guo, De-Qin Wu*Ling Meng*
Affiliation:
- Research Division of Clinical Pharmacology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029,China
- Research Division of Clinical Pharmacology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029,China
Keywords:
MTX, SNP, efficacy, toxicity, pharmacogenomics, polymorphisms.
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.
