By using the MDR (Multifactor Dimensionality Reduction) method, a cohort of 255 RA patients treated with MTX in the USA was evaluated with the efficacy of MTX treatment, and the results showed that 53% MTX responders was associated with high-order interactions among SNPs in ITPA (C94A), RFC1 (G80A), and ATIC (C347G) genes46. This evidence concerns the gene RFC1 and rheumatoid arthritis.