Laboratory of Research in Applied Immunology, State University of Londrina, Londrina, PR, Brazil.
Outpatient Clinic of Gastroenterology, University Hospital, State University of Londrina, Londrina, PR, Brazil.
Int J Colorectal Dis. 2021 Feb;36(2):383-393. doi: 10.1007/s00384-020-03743-3. Epub 2020 Oct 12.
The aim of the present study was to evaluate the IL6 -174 G>C (rs1800795) and -572 G>C (rs1800796) genetic variants and their association with inflammatory bowel diseases (IBDs), disease activity, and response to TNF-α inhibitors.
The study included 178 patients with IBD and 224 healthy controls. Among the IBD patients, 66 of them were in use of TNF-α inhibitors therapy and were followed during 48 weeks and categorized as responders and non-responders.
In total, 89 (50.0%) had ulcerative colitis (UC) and 89 (50.0%) had Crohn's disease (CD). The IL6 -572 CC genotype presented a protective effect in CD patients in codominant and recessive models, while the IL6 -174 CC genotype was associated with susceptibility to UC and CD. The presence of G/C haplotype in the recessive model (GCGC) was associated with UC. The Crohn's disease endoscopic index of severity was low in those patients carrying the GCGC haplotype. It was observed that there was no association between the IL6 genetic variants and TNF-α inhibitor therapy response.
The G/C haplotype (recessive model) was associated with susceptibility to UC but not to CD. However, the G/C haplotype (dominant model) was associated with the endoscopic activity of CD. Moreover, these IL6 variants did not predict the TNF-α inhibitor therapy response.
本研究旨在评估 IL6-174G>C(rs1800795)和-572G>C(rs1800796)遗传变异及其与炎症性肠病（IBD）、疾病活动度和对 TNF-α 抑制剂的反应的关系。
本研究纳入了 178 例 IBD 患者和 224 名健康对照者。在 IBD 患者中，66 例正在接受 TNF-α 抑制剂治疗，并在 48 周内进行了随访，分为应答者和无应答者。
总共有 89 例（50.0%）患有溃疡性结肠炎（UC），89 例（50.0%）患有克罗恩病（CD）。在 CD 患者中，IL6-572CC 基因型在共显性和隐性模型中均表现出保护作用，而 IL6-174CC 基因型与 UC 和 CD 的易感性相关。在隐性模型中，G/C 单倍型的存在（GCGC）与 UC 相关。携带 GCGC 单倍型的 CD 患者的克罗恩病内镜严重程度指数较低。观察到，IL6 遗传变异与 TNF-α 抑制剂治疗反应之间没有关联。
G/C 单倍型（隐性模型）与 UC 的易感性相关，但与 CD 无关。然而，G/C 单倍型（显性模型）与 CD 的内镜活动度相关。此外，这些 IL6 变体不能预测 TNF-α 抑制剂治疗反应。
