434
Views
0
CrossRef citations to date
0
Altmetric
ORIGINAL RESEARCH

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

, , , , , , , & ORCID Icon show all
Pages 407-423 | Received 15 Jan 2023, Accepted 24 Apr 2023, Published online: 02 May 2023
 

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.

Ethics Statement

This study was approved by the Ethics Committee of Ningbo First Hospital and written informed consent was obtained from all participants. Subject identification information was not disclosed in the study, and patients were identified by numbers to indicate.

Acknowledgments

This research was supported by the Natural Science Foundation of Ningbo (No. 2021J037), the 3315 Innovation Team Foundation of Ningbo (No.2019A-14-C) and Special Research Assistant Program of the Chinese Academy of Sciences.

Disclosure

The authors report no conflicts of interest in this work.