MTX is originally designed as a folate pathway antagonist by inhibiting dihydrofolate reductase (DHFR) when given at very high doses for leukemia (as high as 1 g in a single dose), but it is found that the drug was effective in RA patients when using it at much lower doses (15–25 mg weekly) [9,10]. This evidence concerns the gene DHFR and rheumatoid arthritis.