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MTHFR functional genetic variation and methotrexate treatment response in rheumatoid arthritis: a meta-analysis
Michael D Morgan1, Nashwa Al-Shaarawy, Steve Martin
1Leeds Institute of Rheumatic & Musculoskeletal Medicine, Wellcome Trust Brenner Building, St James's University Hospital, Beckett Street, Leeds, West Yorkshire, LS9 7TF, UK.
Aim:
To date, functional MTHFR SNPs have been tested for their impact on low-dose methotrexate (MTX) response in small rheumatoid arthritis (RA) cohorts. We sought to test their effect in the single largest cohort studied to date, and undertook a meta-analysis utilizing stringent study inclusion criteria.
Materials & Methods:
RA patients treated with MTX monotherapy from the Yorkshire Early Arthritis Register (YEAR) were genotyped using RFLP assays, and tested for association with treatment efficacy. Studies for meta-analysis were screened by a set of stringent inclusion criteria.
Results & Conclusion:
rs1801131 and rs1801133 were not associated with response to MTX in the YEAR cohort, nor did they affect the probability of achieving a low disease activity state. A meta-analysis of comparable studies found no association with these SNPs. MTHFR SNPs rs1801131 and rs1801133 are unlikely to have a clinically meaningful effect on the first 6 months of MTX treatment in early RA.
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