Lupus disease activity state and Foxp3 gene polymorphism

The autoimmune disease systemic lupus erythematosus (SLE) is presented with many clinical symptoms. The transcription factor fork head box protein 3 (Foxp3) is expressed on regulatory T (T-reg) cells and essential for its development and function. Functional single-nucleotide polymorphisms (SNPs) in the Foxp3-3279 (rs3761548 C/A) gene influence SLE pathogenesis. We aimed to assess the relation between the functional polymorphism in Foxp3-3279 (rs3761548 C/A) gene and risk of SLE development and lupus disease activity state. This case-control study included SLE patients, diagnosed according to American College of Rheumatology/Systemic Lupus International Collaborating Clinics (ACR/SLICC) classification criteria. The degree of disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS). Foxp3-3279 (rs3761548 C/A) gene polymorphism was detected using the polymerase chain reaction restriction fragment length polymorphism-based analysis (PCR-RFLP). We found that AA and AC genotypes significantly increased the risk of SLE by 7.25 and 2.88 folds, respectively (p < 0.001) and A allele significantly increased that risk by 3.12 folds (p < 0.001). AA genotype significantly increased the risk of SLE moderate-severe disease activity and risk of lupus nephritis by 33.6 folds (p < 0.001). In conclusion, Foxp3 -3279 (rs3761548 C/A) gene polymorphism was associated with the risk of SLE and lupus nephritis. The relation of this SNP with SLE disease activity highlighted the role of Foxp3 gene in SLE pathogenesis and manifestations that could potentially enhance the management of SLE patients by identifying each person's unique response to treatment.