MTHFR and MTRR Genetic Polymorphism of Methotrexate Therapy Outcomes in Early Rheumatoid Arthritis

Qian Zhang; Pan Fu; Zhanglei Cao; Hua Huang; Qinwen Wen; Kaizhe Wang; Tong Kong; Xiudi Wu; Jianping Zheng

doi:10.2147/PGPM.S404949

MTHFR and MTRR Genetic Polymorphism of Methotrexate Therapy Outcomes in Early Rheumatoid Arthritis

Pharmgenomics Pers Med. 2023 May 2:16:407-423. doi: 10.2147/PGPM.S404949. eCollection 2023.

Authors

Qian Zhang^{1

2}, Pan Fu², Zhanglei Cao², Hua Huang³, Qinwen Wen³, Kaizhe Wang², Tong Kong², Xiudi Wu³, Jianping Zheng²

Affiliations

¹ Jiangxi 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.
² Cixi Institute of Biomedical Engineering, Ningbo Institute of Materials Technology & Engineering, Chinese Academy of Sciences (CAS), Ningbo, 315300, People's Republic of China.
³ Department of Rheumatology and Immunology, Ningbo First Hospital, Ningbo, 315010, People's Republic of China.

Abstract

Purpose: 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 and non-response groups.

Conclusion: Our findings suggest that the MTHFR C677T, MTHFR A1298C and MTRR A66G polymorphisms may not predict MTX clinical treatment response and disease activity in patients with early RA. The study revealed that smoke, alcohol, and males were possible influential factors for MTX non-response.

Keywords: DAS28; MTHFR; MTRR; methotrexate; rheumatoid arthritis.