Genetic variants of pre-miRNA-499a and oxidative-immune biomarkers predict disease severity in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and oxidative stress (OS). This study investigated whether pre-miRNA-499a (rs3746444) and pre-miRNA-146a (rs2910164) polymorphisms are associated with RA susceptibility and disease severity, and evaluated OS/antioxidant and inflammatory profiles in relation to disease activity score 28 based on erythrocyte sedimentation rate (DAS28‑ESR) and anti–cyclic citrullinated peptide (anti-CCP)in an Erbil-based cohort. Fifty RA patients and fifty healthy controls were genotyped by amplification refractory mutation system (ARMS-PCR). Serum OS and antioxidant markers, inflammatory cytokines, and trace elements were assessed, and their relationships with DAS28‑ESR and anti-CCP were analyzed. The rs3746444 TC genotype was significantly associated with increased RA risk (odds ratio (OR) = 2.708, p = 0.0209) and with higher DAS28‑ESR and anti-CCP levels (p = 0.020), whereas rs2910164 showed no significant association. RA patients demonstrated a disturbed redox balance and inflammatory activation compared with controls. Among the measured variables, interferon (IFN)-γ was the strongest predictor of both disease activity and anti-CCP titers (p < 0.001), with interleukin (IL)-10 and superoxide dismutase (SOD) showing an inverse relationship. pre-miRNA-499a rs3746444, particularly the TC genotype, is linked to RA susceptibility and greater disease severity in this population. IFN-γ, together with key antioxidant/inflammatory indicators, may support monitoring of RA activity and stratification of patients for more tailored management.