Promoter Methylation of MMP9 and RUNX3: Diagnostic Potential and Clinical Associations in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and joint damage. Conventional diagnostic markers for RA have limitations, prompting the exploration of DNA methylation analysis as a potential biomarker. This study focuses on evaluating the methylation levels of two genes, MMP9 and RUNX3, in peripheral blood mononuclear cells (PBMCs) as potential biomarkers for RA.

We assessed the methylation levels of the MMP9 and RUNX3 promoters in PBMCs from 72 RA patients and 72 healthy controls using the methylation-quantification of endonuclease-resistant DNA (MethyQESD) method. The data were analyzed for diagnostic utility and correlation with clinical features, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).

MMP9 methylation levels were significantly lower in RA patients compared to controls (38.23 ± 28.62 vs. 62.27 ± 19.68, P < 0.001), indicating significant hypomethylation. RUNX3 methylation showed no significant difference between the groups (P: 0.295). Receiver operating characteristic (ROC) curve analysis revealed a sensitivity of 73.61% and a specificity of 72.22% with an area under the ROC curve of 0.756 (P < 0.001) for MMP9. MMP9 methylation was negatively correlated with ESR and CRP levels (P < 0.001), while RUNX3 showed positive correlations with ESR (P: 0.014) and CRP (P: 0.001).

The study suggests that MMP9 promoter hypomethylation may serve as a promising diagnostic and prognostic biomarker for RA. In addition, RUNX3 promoter methylation showed potential for assessing disease activity. These findings have the potential to improve the diagnosis and prognosis of RA, contributing to improved clinical management of patients.