Altered DNA Methylation Patterns in IFI44L and FOXP3 Genes in Patients with Rheumatoid Arthritis: A Case-Control Study
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Delnya Gholami1, Zahra Ourang2,3, Mohammad Saatchi4,5
1Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Background:
Epigenetic modifications, particularly DNA methylation, are implicated in the pathogenesis of rheumatoid arthritis (RA). This study 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 levels were quantified using MethyQESD (dual enzymatic digestion followed by real-time PCR). Group differences were analyzed with non-parametric tests; diagnostic performance was evaluated by receiver operating characteristic (ROC) curve analysis.
Results:
FOXP3 promoter methylation levels were significantly in RA than in controls (P = 0.026), whereas IFI44L methylation levels were significantly lower in RA (P< 0.0001) and showed strong diagnostic performance (AUC 0.811; P< 0.001). No significant difference in TET2 methylation was observed between groups. In RA patients, FOXP3 and TET2 methylation levels were positively correlated with C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), while IFI44L methylation was negatively correlated.
Conclusions:
IFI44L methylation levels in peripheral blood may serve as a promising potential diagnostic biomarker for RA. The associations of FOXP3, TET2, and IFI44L methylation levels with CRP and ESR suggest potential roles in RA-related inflammatory processes.