Altered DNA Methylation Patterns in IFI44L and FOXP3 Genes in Patients with Rheumatoid Arthritis: A Case-Control Study

Objective: Epigenetic modifications, particularly DNA methylation, are implicated in the pathogenesis of rheumatoid arthritis (RA). We assessed the diagnostic utility of FOXP3, TET2, and IFI44L methylation in peripheral blood and examined their associations with inflammatory markers. Methods: We enrolled 100 patients with RA and 105 healthy controls. Clinical and laboratory data were recorded. DNA methylation at FOXP3, TET2, and IFI44L was quantified using MethyQESD (dual enzymatic digestion followed by real-time PCR). Group differences were analyzed with non-parametric tests; diagnostic performance was evaluated by ROC analysis. Results: FOXP3 promoter methylation was higher in RA than in controls (P = 0.026), whereas IFI44L methylation was lower in RA (P < 0.0001) and showed strong diagnostic performance (AUC 0.811; P < 0.001). TET2 methylation did not differ between groups. In RA, FOXP3 and TET2 methylation correlated positively with CRP and ESR, while IFI44L methylation correlated negatively with these markers Conclusion: IFI44L methylation levels in peripheral blood may serve as a promising diagnostic biomarker for RA. The associations of FOXP3, TET2, and IFI44L methylation with CRP and ESR suggest potential roles in RA-related inflammation.