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


Xiao, H and Xu, J and Zhou, X and Stankovich, J and Pan, F and Zhang, Z and Xu, S and Lian, L and Ding, C, Associations between the genetic polymorphisms of MTHFR and outcomes of methotrexate treatment in rheumatoid arthritis, Clinical and Experimental Rheumatology, 28, (5) pp. 728-733. ISSN 0392-856X (2010) [Refereed Article]

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Copyright © 2010 Clinical and Experimental Rheumatology

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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.

Item Details

Item Type:Refereed Article
Keywords:5, 10-methylenetetrahydrofolate reductase, genetic polymorphisms, clinical response, adverse events, rheumatoid arthritis
Research Division:Biomedical and Clinical Sciences
Research Group:Clinical sciences
Research Field:Rheumatology and arthritis
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Stankovich, J (Dr Jim Stankovich)
UTAS Author:Ding, C (Professor Chang-Hai Ding)
ID Code:66035
Year Published:2010
Web of Science® Times Cited:26
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-12-16
Last Modified:2013-10-28
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