Allele frequencies in the 677, 1298 and 3 additional SNPs in the MTHFR coding region in 223 (193 Caucasians and 30 African-Americans) patients with rheumatoid arthritis who previously participated in one of two prospective clinical trials were characterised, and genotypes were correlated with the efficacy and toxicity of MTX.
Although a small sample study, our findings do not suggest a significant association of MTHFR/TS allele/genotype with MTX response in our ethnically distinct Indian (Asian) RA patients.
Associations between asymmetric dimethylarginine, homocysteine, and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133) in rheumatoid arthritis.
Associations between MTX response in RA patients in MTHFR 1298A > C (rs1801131), ATIC 347C > G (rs2372536), RFC-1 80G > A (rs1051266), SLC19A1 A > G (rs2838956) and SLC19A1 G > A (rs7499) genetic polymorphisms were found, but not observed between the MTHFR 677C > T (rs1801133), TYMS 28 bp VNTR (rs34743033), MTRR 66A > G (rs1801394), and ABCB1 3435C > T (rs1045642).
Cardiovascular events are not associated with MTHFR polymorphisms, but are associated with methotrexate use and traditional risk factors in US veterans with rheumatoid arthritis.
Frequencies of MTHFRC677T and A1298C were similar to those reported in Japanese RA patients, while frequencies of RFC-1 G80A genotypes differed from those reported in RA patients in the United States.
Genetic factors are also important in the treatment of RA because the activity of enzymes relevant in the metabolism of drugs such as methotrexate and azathioprine, including methylenetetrahydrofolate reductase and thiopurine methyltransferase, are in part genetically determined.
Given the paucity of studies, especially in non-Asian populations, further studies with larger sample sizes are required to elucidate the role of MTHFR polymorphisms in the genetic basis of RA in different ethnic populations.
Higher serum B12 levels and decreased frequency of the MTHFR 677TT variant in RA patients could potentially account for the observed differences between the groups.
In addition to the strong association between alleles of the HLA-DRB1*04 shared epitope and both subclinical and clinically evident CV disease, genes implicated in inflammation and metabolism, such as TNFA, MTHFR, and CCR5, seem to be associated with a higher risk of CV disease in patients with RA.
In this regard, besides a strong association between the HLA-DRB1∗04 shared epitope alleles and both endothelial dysfunction, an early step in the atherosclerotic process, and clinically evident CV disease, other polymorphisms belonging to genes implicated in inflammatory and metabolic pathways, located inside and outside the HLA region, such as the 308 variant (G > A, rs1800629) of the TNFA locus, the rs1801131 polymorphism (A > C; position + 1298) of the MTHFR locus, or a deletion of 32 base pairs on the CCR5 gene, seem to be associated with the risk of CV disease in patients with RA.
In this study, the six polymorphisms associated with rheumatoid arthritis (RA), N-acetyltransferase2 (NAT2) gene polymorphisms T341C, G590A, and G857A, methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms C677T and A1298C, and serum amyloid A1 (SAA1) gene promoter polymorphism C-13T were simultaneously detected by the electrochemical DNA chip and the loop-mediated isothermal amplification (LAMP) method, which is a novel technique for DNA amplification.
MEDLINE and EMBASE database searches and subsequent manual searches were utilized to identify articles in which C677T and A1298CMTHFR polymorphisms were evaluated in RA patients taking MTX.
Meta-analysis did not show any association between the C677T and A1298C polymorphisms of MTHFR and the toxicity of methotrexate in RA in all patients or in Asian patients.
Our findings suggest that C677T polymorphism in the MTHFR gene is not predictive of toxicity or efficacy of MTX treatment in RA patients receiving folate supplementation.
Our study suggests that MTHFRC677T and ATIC T675C genotyping combined with clinicopathological data may help to identify patients whom will not benefit from MTX treatment and, therefore, assist clinicians in personalizing RA treatment.
Polymorphisms C677T and A1298C in the MTHFR gene in Mexican patients with rheumatoid arthritis treated with methotrexate: implication with elevation of transaminases.
Polymorphisms in the thymidylate synthase and methylenetetrahydrofolate reductase genes and sensitivity to the low-dose methotrexate therapy in patients with rheumatoid arthritis.