Gene polymorphisms are suggested to affect the incidence of MTX-related toxicity, as several studies show that MTHFR c.667C>T, MTHFR c.1298A>C, and ATIC c.347C>G are the most common genes responsible for MTX toxicity, in both the treatment of SLE and other diseases including RA. This evidence concerns the gene MTHFR and systemic lupus erythematosus.