We comprehensively investigated the allelic frequencies in the gene polymorphisms of enzymes and transporter proteins including MTHFR, TYMS, RFC1, FPGS, GGH, ABCB1, ABCC2 and ABCG2, which affect MTX pharmacokinetics and the therapeutic response to it, between a healthy Japanese population and Japanese RA patients to obtain the fundamental data for the personalized MTX therapy for RA. The gene discussed is MTHFR; the disease is rheumatoid arthritis.