Pharmacogenetic approach to methotrexate-related toxicity prediction in psoriasis

Abstract

Methotrexate is a highly effective for psoriasis, but the use of methotrexate may be limited by its adverse effects. Approximately 1030% of patients treated with methotrexate experience adverse drug reactions, leading to the therapy discontinuation. Patient genetics can play a significant role in the interindividual variability of drug response. There is a growing body of literature on allelic variants of various genes that are assosiated with methotrexate toxicity. Pharmacogenetic studies may establish how patients genotype affect the safety of methotrexate. Treatment Data shows that to predict the risk of methotrexate-induced toxicity it is necessary to take into account the interindividual variability in methotrexate pharmacokinetics, which may be determined by the presence of single-nucleotide polymorphisms of genes encoding methotrexate carrier proteins and enzymes of its biotransformation. The activity of transporter proteins affects the drugs in the blood plasma and peripheral tissues, thereby determining its toxicity. The review was aimed is to summarize the current knowledge on pharmacogenetic polymorphisms that may affect the variability of methotrexate-related toxicity. Evaluation of such promising candidates for predictors of methotrexate-related toxicity risk could be used in psoriasis treatment personalization.