Response to Methotrexate in RA May Be Predicted by Gene Expression

HealthDay News — For patients with rheumatoid arthritis (RA), increased baseline gene expression of p21, caspase 3, and runt-related transcription factor (RUNX)2 in the peripheral blood may be associated with improved clinical response to methotrexate (MTX), according to a study published online in the International Journal of Rheumatic Diseases.

Elena V. Tchetina, PhD, from the Nasonova Research Institute of Rheumatology in Moscow, and colleagues examined 26 control subjects and 40 patients with RA to determine the potential of baseline gene expression in the whole blood of disease-modifying anti-rheumatic drug-naive RA patients for predicting response to MTX.

The researchers found that significant increases in joint space narrowing score (JSN) accompanied decreases in disease activity at the end of the study. Expressions of the Unc-51-like kinase1 (ULK1) and matrix metalloproteinase (MMP-9) genes were positively associated with the level of C-reactive protein; MMP-9 expression correlated with Disease Activity Score of 28 joints (DAS28) and swollen joint count. 

There was a positive correlation for baseline tumor necrosis factor α gene expression with JSN at the end of follow-up, while correlations were seen for p21, caspase 3, and RUNX2 with ΔDAS28 values.

“Our results suggest that the expressions of MMP-9 and ULK1 might be associated with disease activity,” the authors write. “Increased baseline gene expressions of RUNX2, p21, and caspase 3 in the peripheral blood might predict better responses to MTX therapy.”

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Tchetina EV, Demidova NV, Markova GA, Taskina EA, Glukhova SI, Karateev DE. Increased baseline RUNX2, caspase 3 and p21 gene expressions in the peripheral blood of disease-modifying anti-rheumatic drug-naïve rheumatoid arthritis patients are associated with improved clinical response to methotrexate therapy [published online July 25, 2017]. Int J Rheum Dis. doi:10.1111/1756-185X.13131