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MTX Toxicity - MTHFR

Clinical Features

Methotrexate (MTX) is a therapeutic agent commonly used to treat malignant and immune illnesses. Pharmacologically, it interacts with folate metabolism, especially the enzyme Methylenetetrahydrofolate reductase (MTHFR). A mutation at nucleotide position 677 (c.677C>T) in the MTHFR gene leads to decreased enzyme activity, with a remaining activity of 60% in heterozygote form and of 35% in homozygote form. First and foremost, carriers of a homozygous mutation can suffer a toxic reaction to a course of MTX.

By determining a person's MTHFR genotype prior to a planned MTX therapy, the risk of possible MTX poisoning can be identified and the dose adjusted accordingly.

Genetic Information

A study by Schmeling et al. (2005) determined that the side-effects of MTX therapy occur more often in patients with a heterozygosity for the genotype c.677C>T than in patients with the common genotype c.677C (69% versus 47%). Persons with the c.677T genotype thus have a markedly higher risk of suffering side-effects while undergoing MTX therapy.

Diagnostic