Genetic Polymorphism & Methotrexate Therapy Outcomes in Rheumatoid Arthritis

Abstract

Methotrexate (MTX) is commonly used as a disease-modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). Genetic polymorphisms in key enzymes involved in MTX metabolism, such as methyl tetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR), have been studied for their potential impact on MTX therapy outcomes in early RA patients. Zhang et al investigated a population of 32 patients in East China with early RA fulfilling the diagnostic standards of the American College of Rheumatology (ACR) was enrolled, and 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. The distribution of the three polymorphic genotypes that were studied is in accordance with the Hardy-Weinberg genetic equilibrium. The patient pathology variables smoking (OR = 0.088, P = 0.037), drinking 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. Their 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. Pharmgenomics Pers Med. 2023 May 2;16:407-423.  doi: 10.2147/PGPM.S404949. eCollection 2023.