Associations between the genetic polymorphisms of MTHFR and outcomes of methotrexate treatment in rheumatoid arthritis.

OBJECTIVES: To determine whether 5, 10-methylenetetrahydrofolate reductase (MTHFR) rs1801133C/T, rs1801131A/C, rs2274976A/G, rs2066462C/T genetic polymorphisms are associated with clinical response and adverse effects (AEs) of methotrexate (MTX) treatment in Chinese Han patients with rheumatoid arthritis (RA). METHODS: One hundred and ten RA patients defined by the American College of Rheumatology (ACR) 1987 revised criteria were involved in this study. All patients were treated with low-dose MTX (10-15 mg/week) without concomitant uses of other DMARDs. Clinical response (using ACR20 criteria) and AEs were evaluated at 0, 4, 12, 16 and 24 weeks. The genotypes of MTHFR rs1801133C/T, rs1801131A/C, rs2274976A/G and rs2066462C/T were detected by real-time fluorescent quantitative PCR. RESULTS: The allele frequency of rs1801131C in the clinical response group was higher than in the non-response group (21.0% vs. 8.1%, p<0.05), and the patients with CC or AC genotype had greater clinical response than those with AA genotype. The allele frequencies of rs1801133T and rs2274976A were higher in the group with AEs than that without AEs (56.4% vs. 37.5% and 14.9% vs. 4.2%, respectively, both p<0.05). The patients with CT or TT genotype in rs1801133 had higher risks of AEs than those with CC genotype. CONCLUSIONS: While rs1801131A/C genetic polymorphism is associated with the clinical response, rs1801133C/T and rs2274976A/G genetic polymorphisms are associated with MTX-related AEs in the treatment of RA. This suggests individualisation is necessary to achieve optimal outcomes in MTX therapy of RA.