Upregulation of microRNA-93-5p/microRNA-4668-5p, and promoter methylation of matrix metalloproteinase-3 and interleukin-16 genes in Turkish patients with rheumatoid arthritis

Abstract Aim of the work To investigate promoter methylation of matrix metalloproteinase-3 (MMP-3) and interleukin-16 (IL-16) genes with the expression of miRNA-93-5p and miRNA-4668-5p which target these genes in rheumatoid arthritis (RA), respectively. Patients and methods The study included 49 RA patients and 38 healthy controls. Promoter methylation of MMP-3 and IL-16 was analyzed by methylation-specific PCR. The expression of miRNA-93-5p and miRNA-4668-5p were determined. Disease activity score (DAS28) was assessed. Results The 49 patients (38 female, 11 male) mean age was 50.4 ± 10.5 years and disease duration of 9.1 ± 7.4 years. The mean DAS28 was 3.9 ± 1.4. The MMP-3 gene methylation frequency was significantly lower in patients (n = 37;75.5%) compared to control (n = 37;97.4%) (p = 0.004) while they were comparable for IL-16 gene (n = 46;93.9% vs n = 37;97.4%)(p = 0.45). The relative normalized expression of miRNA-93-5p and miRNA-4668-5p were significantly increased (p  Conclusions The methylation status of MMP-3 promoter and expression levels of miRNA-93-5p and miRNA-4668-5p could be useful biomarkers for the pathogenesis of RA and might reflect disease activity.