Laboratory of Research in Applied Immunology, State University of Londrina, Londrina, PR, Brazil.
Department of Rheumatology, Pontifical Catholic University of Paraná, Londrina, PR, Brazil.
Sci Rep. 2021 Mar 8;11(1):5406. doi: 10.1038/s41598-021-84832-3.
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.
本研究旨在评估 rs2232365（-924G > A）和 rs3761548（-3279C > A）FOXP3 变体与系统性红斑狼疮（SLE）易感性、TGF-β1 血浆水平、自身抗体和狼疮肾炎（LN）以及 SLE 疾病活动指数（SLEDAI）的关联。研究纳入了 196 名女性 SLE 患者和 157 名女性对照。FOXP3 变体通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）确定。TGF-β1 血浆水平采用免疫荧光测定法测定。-3279C > A 中的 AA 基因型 [OR：2.650，95%CI（1.070-6.564），p = 0.035]和 A 等位基因 [OR：2.644，95%CI（1.104-6.333），p = 0.029]与 SLE 诊断相关。A/A 单倍型与 SLE 相关 [OR：3.729，95%CI（1.006-13.820），p = 0.049]。GCGC 单倍型患者的 TGF-β1 水平更高（p = 0.012）。-924AA 基因型患者抗 dsDNA 的频率更高（p = 0.012）和抗 U1RNP（p = 0.036）。A/C 单倍型的 SLEDAI 评分更高 [OR：1.119，95%CI（1.015-1.234），p = 0.024]，ACAC 单倍型抗 dsDNA 的频率更高 [OR：3.026，95%CI（1.062-8.624），p = 0.038]，抗 U1RNP [OR：5.649，95%CI（1.199-26.610），p = 0.029]和肾炎 [OR：2.501，95%CI（1.004-6.229），p = 0.049]。我们的数据表明，G/C 单倍型为 SLE 提供保护。而两种变体的等位基因 A 的存在可能有利于自身免疫、疾病活动和 LN。
