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Qian Zhang,1,2 Pan Fu,2 Zhanglei Cao,2 Hua Huang,3 Qinwen Wen,3 Kaizhe Wang,2 Tong Kong,2 Xiudi Wu,3 Jianping Zheng2 1Jiangxi Key Laboratory for Rare Earths Magnetic Materials and Devices, College of Rare Earths, Jiangxi University of Science and Technology, Ganzhou, 341000, People’s Republic of China; 2Cixi Institute of Biomedical Engineering, Ningbo Institute of Materials Technology & Engineering, Chinese Academy of Sciences (CAS), Ningbo, 315300, People’s Republic of China; 3Department of Rheumatology and Immunology, Ningbo First Hospital, Ningbo, 315010, People’s Republic of ChinaCorrespondence: Jianping Zheng; Xiudi Wu, Tel +86– 18091984088 ; +86– 13857826442, Email zhengjianping@nimte.ac.cn; awu1100@aliyun.comPurpose: Methotrexate (MTX) is used as an anchor drug for the treatment of rheumatoid arthritis (RA) and there may be differences in drug action between genotypes. The purpose of this study was to investigate the relationship between clinical efficacy response and disease activity of MTX monotherapy with methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms.Patients and Methods: In the study, a population of 32 patients in East China with early RA fulfilling the diagnostic standards of the American College of Rheumatology (ACR) were enrolled, all of them received MTX monotherapy. Genotyping of patients MTHFR C677T and A1298C, MTRR A66G using tetra-primer ARMS-PCR method and sanger sequencing to verify its accuracy.Results: The distribution of three polymorphic genotypes that were studied is in accordance with the Hardy-Weinberg genetic equilibrium. The patient pathology variables smoke (OR = 0.088, P = 0.037), drink alcohol (OR = 0.039, P = 0.016) and males (OR = 0.088, P = 0.037) were significantly associated with non-response to MTX. Genotype, allele distribution and genetic statistical models were not found to be related to MTX treatment response and disease activity in both the response groups