Mutations in the methylenetetrahydrofolate reductase (MTHFR) gene are associated with decreased enzyme activity, which leads to hyperhomocysteinemia and toxic side effects of methotrexate therapy. ViennaLab assays identify patients predisposed to develop cardiovascular diseases or intolerance to methotrexate.

MTHFR

• Elevated levels of homocysteine, an intermediary product of the methionine metabolism, are an established risk factor for atherosclerosis and arterial thrombosis.

• Two common variants in the MTHFR gene, 677C>T and 1298A>C, contribute to reduced enzyme activity and thereby to hyperhomocysteinemia.

• Consecutively, hyperhomocysteinemia may affect methotrexate sensitivity and contribute to toxicity.

• Homozygosity for 677C>T or compound heterozygosity for 677C>T / 1298A>C conveys a significantly higher risk for negative side-effects of methotrexate medication.

• Identification of these genetic variants in the MTHFR gene is crucial for an adequate and safe methotrexate therapy.