Laboratory of Research in Applied Immunology, Universidade Estadual de Londrina, Londrina, PR, Brazil; Outpatient Clinic of Gastroenterology, Hospital Universitário, Universidade Estadual de Londrina, Londrina, PR, Brazil.
Laboratory of Research in Applied Immunology, Universidade Estadual de Londrina, Londrina, PR, Brazil.
Clinics (Sao Paulo). 2022 Jul 26;77:100084. doi: 10.1016/j.clinsp.2022.100084. eCollection 2022.
The aim of this study was to evaluate the association of -924 G>A (rs2232365) and -3279 C>A (rs3761548) FOXP3 variants with IBD susceptibility, clinical and endoscopic activity, and IL-10 and TGF-β1 plasma levels.
The study included 110 IBD female patients, 60 with Ulcerative Colitis (UC) and 50 with Crohn's Disease (CD), and 154 female controls. FOXP3 variants were determined with Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Plasma levels of IL-10 and TGF-β1 were determined using immunofluorimetric assay.
AA genotype of rs2232365 and rs3761548 was associated with CD (OR = 3.147, 95% CI 1.015-9.758, p = 0.047) and UC (OR = 3.221, 95% CI 1.050-9.876, p = 0.041) susceptibility, respectively. However, were not associated with TGF-β1 and IL-10 levels, and endoscopic/clinical activity disease. GAGA haplotype was associated with IBD (OR = 4.003, 95% CI 1.100-14.56, p = 0.035) and UC susceptibility (OR = 6.107, 95% CI 1.609-23.18, p = 0.008). In addition, IBD patients with the GAGA haplotype had lower TGF-β1 levels (p = 0.041). Moreover, G/C haplotype (dominant model) had a protective effect of 60% in CD susceptibility and lower Endoscopic Severity Index.
These results suggest that FOXP3 variants could exert a role in the Treg, which could be one of the factors involved in the susceptibility and pathogenesis of IBD.
本研究旨在评估 FOXP3 基因-924 G>A(rs2232365) 和-3279 C>A(rs3761548) 变异与 IBD 易感性、临床和内镜活动以及 IL-10 和 TGF-β1 血浆水平的关联。
本研究纳入了 110 例 IBD 女性患者，其中 60 例为溃疡性结肠炎（UC）患者，50 例为克罗恩病（CD）患者，以及 154 例女性对照。FOXP3 变异通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）进行确定。使用免疫荧光测定法测定 IL-10 和 TGF-β1 的血浆水平。
rs2232365 和 rs3761548 的 AA 基因型分别与 CD（OR=3.147，95%CI 1.015-9.758，p=0.047）和 UC（OR=3.221，95%CI 1.050-9.876，p=0.041）易感性相关。然而，它们与 TGF-β1 和 IL-10 水平以及内镜/临床活动疾病无关。GAGA 单倍型与 IBD（OR=4.003，95%CI 1.100-14.56，p=0.035）和 UC 易感性（OR=6.107，95%CI 1.609-23.18，p=0.008）相关。此外，携带 GAGA 单倍型的 IBD 患者 TGF-β1 水平较低（p=0.041）。此外，G/C 单倍型（显性模型）在 CD 易感性中具有 60%的保护作用，并降低内镜严重程度指数。
这些结果表明，FOXP3 变异可能在 Treg 中发挥作用，这可能是 IBD 易感性和发病机制的因素之一。
