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The aim of this study was to evaluate the association of rs2232365 (-924 G > A) and rs3761548 (-3279 C > A)  FOXP3  variants with systemic lupus erythematosus (SLE) susceptibility, TGF-β1 plasma levels, autoantibodies, and LN nephritis, and SLE disease activity index (SLEDAI). The study included 196 SLE female patients and 157 female controls.  FOXP3  variants were determined with polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP). Plasma levels of TGF-β1 were determined using immunofluorimetric assay. The AA genotype [OR: 2.650, CI 95%(1.070–6.564),  p  = 0.035] and A allele [OR: 2.644, CI 95%(1.104–6.333),  p  = 0.029] were associated with SLE diagnosis in the -3279 C > A. The A/A haplotype was associated with SLE [OR: 3.729, CI 95%(1.006–13.820),  p  = 0.049]. GCGC haplotype patients had higher TGF-β1 levels ( p  = 0.012) than other haplotypes. Patients with -924 AA genotype showed higher frequency of anti-dsDNA ( p  = 0.012) and anti-U1RNP ( p  = 0.036). The A/C haplotype had higher SLEDAI score [OR: 1.119, CI 95%(1.015–1.234),  p  = 0.024] and ACAC haplotype higher frequency of anti-dsDNA [OR: 3.026, CI 95%(1.062–8.624),  p  = 0.038], anti-U1RNP [OR: 5.649, CI 95%(1.199–26.610),  p  = 0.029] and nephritis [OR: 2.501, CI 95%(1.004–6.229),  p  = 0.049]. Our data demonstrate that the G/C haplotype provides protection for SLE. While the presence of allele A of both variants could favor autoimmunity, disease activity, and LN.

Haplotypes of FOXP3 genetic variants are associated with susceptibility, autoantibodies, and TGF-β1 in patients with systemic lupus erythematosus