Abstract
Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease in which genetic factors play a critical role, and emerging evidence suggests that variants in the signal transducer and activator of transcription 4 (STAT4) gene may influence both susceptibility to the disease and the severity of its clinical expression.
Objectives: This study aimed to investigate the association between STAT4 genetic polymorphisms and the risk of developing RA, as well as their potential influence on disease activity.
Materials and Methods: This case–control study was conducted on 186 RA patients and 192 age‑ and sex‑matched healthy controls from June 12, 2025, to January 16, 2026, at Baghdad Medical City Hospital in Baghdad, Iraq. Demographic and clinical data were collected, and disease activity was assessed using the disease activity score in 28 joints (DAS28). Peripheral blood samples were obtained for genomic DNA extraction using silica‑membrane spin column kits, and STAT4 polymorphisms (rs7574865 and rs10181656) were genotyped by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). The association between STAT4 genetic polymorphisms and the risk of developing RA, as well as disease severity, was evaluated using statistical analysis.
Results: The results indicated that STAT4 gene variants showed strong associations with RA susceptibility: for rs7574865, the GT and TT genotypes compared to GG were linked to higher risk (OR = 1.69 and OR = 3.06, respectively), and for rs10181656, the CG and GG genotypes compared to CC similarly increased risk (OR = 1.66 and OR = 2.62). Among RA patients, DAS28 scores differed significantly across STAT4 genotypes, with higher scores observed in carriers of the risk‑associated alleles for both polymorphisms.
Conclusion: STAT4 polymorphisms, particularly rs7574865 and rs10181656, were significantly associated with increased RA susceptibility and higher disease severity, highlighting their potential value as genetic markers in RA.