The C677T mutation in the methylenetetrahydrofolate reductase gene: A genetic risk factor for methotrexate-related elevation of liver enzymes in rheumatoid arthritis patients

Abstract

The C677T mutation is the first identified genetic risk factor for elevated alanine aminotransferase values during MTX treatment in patients with RA. We postulate that the incidence of clinically important elevation of liver enzyme levels during MTX treatment is mediated by homocysteine metabolism. Supplementation with folic or folinic acid reduced the risk of toxicity-related discontinuation of MTX treatment both in patients with and in patients without the mutation.