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. 2018 May 9;8(1):7342.
doi: 10.1038/s41598-018-25634-y.

Replication Study of Polymorphisms Associated With Response to Methotrexate in Patients With Rheumatoid Arthritis

Free PMC article

Replication Study of Polymorphisms Associated With Response to Methotrexate in Patients With Rheumatoid Arthritis

Rosario López-Rodríguez et al. Sci Rep. .
Free PMC article


About 70 genetic studies have already addressed the need of biomarkers to predict the response of patients with rheumatoid arthritis (RA) to methotrexate (MTX) treatment. However, no genetic biomarker has yet been sufficiently validated. Here, we aimed to replicate a selection of 25 SNPs in the largest collection of patients up to date, which consisted of 915 patients treated with MTX. The change in disease activity (measured as ΔDAS28) from baseline was considered the primary outcome. In addition, response according to widely used criteria (EULAR) was taken as secondary outcome. We considered consistency between outcomes, P values accounting for the number of SNPs, and independence from potential confounders for interpretation of the results. Only the rs1801394 SNP in MTRR fulfilled the high association standards. Its minor allele was associated with less improvement than the major allele according to ΔDAS28 (p = 0.0016), and EULAR response (p = 0.004), with independence of sex, age, baseline DAS28, smoking, seropositivity, concomitant corticosteroid use or previous treatments. In addition, previous evidence suggests the association of this SNP with response to MTX in another autoimmune disease, juvenile idiopathic arthritis, and with high intracellular folate levels, which could contribute to poor response.

Conflict of interest statement

The authors declare no competing interests.


Figure 1
Figure 1
Forest plot of the fixed effects metaanalysis for association of rs1801394 with ΔDAS28 in patients with RA treated with MTX. Square areas are proportional to the weight of the population according to the inverse variance method. Width of the diamond represents the 95% CI of the summary regression coefficient.

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