MTRR A66G, RFC1 G80A, and MTHFR C677T and A1298C Polymorphisms and Disease Activity in Mexicans with Rheumatoid Arthritis Treated with Methotrexate

Abstract

Aim: To investigate the relationships of polymorphisms in genes whose protein products are related in the metabolic pathway of folic acid, particularly MTRR A66G, RFC1 G80A, and MTHFR C677T and A1298C, and disease activity in Mexican patients with rheumatoid arthritis (RA) treated with methotrexate (MTX).Materials and Methods: Sixty-eight patients with RA were included in the study who were being treated with MTX, either with or without other drugs. In addition to general data, disease activity was measured by the disease activity score 28 (DAS28). Single nucleotide polymorphisms (SNPs) genotyping was performed by allelic discrimination using real-time polymerase chain reaction.Results: Differences in genotype (homozygotic or heterozygotic for each allele), allele distributions, and phenotype were not statistically different between the RA group and control populations. We did not find any association between the studied polymorphisms and disease activity nor with the intragroup variables (e.g., clinical activity, body mass index, and single- or combined-drug treatment) or between genetic markers; we also did not find any association within the RA group or between the RA group and control populations.Conclusion: Additional studies of more polymorphisms related to this or other metabolic pathways are required to determine the influence of genetics on disease activity in RA.

Association of MTHFR and RFC1 gene polymorphisms with methotrexate efficacy and toxicity in Chinese Han patients with rheumatoid arthritis

“…In the present study, we detected no difference in genotypes and allele frequencies of MTHFR C677T and A1298C and RFC-1 A80G between patients with RA (cases) and controls, indicating that these polymorphisms were not associated with RA susceptibility in the Henan Han population, consistent with the results of Gonzalez-Mercado et al. 15 and Hashiguchi et al. 16 …”

“…However, few studies have examined the relationship between RFC-1 SNP and RA. In the present study, we detected no difference in genotypes and allele frequencies of MTHFR C677T and A1298C and RFC-1 A80G between patients with RA (cases) and controls, indicating that these polymorphisms were not associated with RA susceptibility in the Henan Han population, consistent with the results of Gonzalez-Mercado et al 15 and Hashiguchi et al 16 MTX, as a DMARD, is the first-line anchor drug for treating RA. It plays a role in the folate transport pathway by inhibiting the key enzymes.…”

Severe Adverse Toxic Effects of Low-Dose Methotrexate Treatment on an Ectopic Pregnancy Patient With Methylenetetrahydrofolate Reductase Mutations: A Case Report

“…Two of the most investigated polymorphisms within the MTHFR gene are single nucleotide polymorphisms (SNPs) at the mRNA positions 677 (rs1801133) and 1,298 (rs1801131) ( 8 ). However, these findings were mainly found in the patients with rheumatoid arthritis or the hematological malignancies ( 14 – 16 , 27 ). This is the first report on serious adverse toxic effects of LD-MTX on an EP patient with MTHFR mutations.…”

Genetic Polymorphisms of TYMS, MTHFR, ATIC, MTR, and MTRR Are Related to the Outcome of Methotrexate Therapy for Rheumatoid Arthritis in a Chinese Population

“…In the Netherlands, no associations between the MTRR and MTR gene polymorphisms and good clinical responses were found in recent-onset RA patients ( Wessels et al, 2006 ). A study ( Gonzalez-Mercado et al, 2017 ) of 110 Mexican RA patients who were diagnosed at least 1 year previously and had been receiving MTX for at least 3 months showed no association between MTRR gene polymorphism and MTX efficacy. Another study ( Lopez-Rodriguez et al, 2018 ) of European Caucasian RA patients showed that MTRR fulfilled the high association standards.…”