A Polymorphism in Interleukin-1β Gene Is Associated with the Development of Pouchitis in Japanese Patients with Ulcerative Colitis
A Polymorphism in Interleukin-1β Gene Is Associated with the Development of Pouchitis in Japanese Patients with Ulcerative Colitis
复制标题
DOI：
10.1159/000503283
复制
发表时间：
2021-05-01
期刊：
影响因子：
3.2
通讯作者：
Ishihara, Soichiro
中科院分区：
文献类型：
--
作者：
Okada, Satoshi;Hata, Keisuke;Ishihara, Soichiro
背景：溃疡性结肠炎（UC）患者的主要并发症包括UC相关癌（UCAC）和术后结肠袋炎。我们的目的是确定与UCAC/高度异型增生（HGD）和结肠袋炎相关的SNP。方法：纳入接受回肠贮袋-肛门吻合术（IPAA）且贮袋功能恢复后随访时间>2年的UC患者。根据改良的结肠袋炎疾病活动指数，至少进行一次袋镜检查以诊断结肠袋炎。对8个据报道与UCAC和结肠袋炎相关的SNP进行SNP基因分型，即：（rs7329174），FCGR2A，（rs 1801274），白细胞介素-1 β（IL-1B; rs1143627）、ITLN 1（rs2274910）、MHC（rs7765379）、TNF α（rs1799964）、TNFSF 15（rs3810936）和UHMK 1（rs768910）。我们研究了这些SNPs与UCAC/HGD和结肠袋炎的关联。回顾性收集患者的背景资料，包括术前肠外表现（EIM）的存在。结果：共纳入91例日本UC患者。在我们的队列中，8个SNPs中没有一个与UCAC/HGD相关。多变量分析证明，术前EIM（风险比[HR] 3.313，95% CI 1.325-8.289）和IL-1B（rs 1143627）TT基因型（HR 2.425，95% CI 1.049-5.61）的存在是总体结肠袋炎发展的独立预测因素。术前存在EIM（HR 3.977，95% CI 1.292-12.24）和IL-1B（rs 1143627 TT基因型; HR 3.382，95% CI 1.101-10.39）也是慢性结肠袋炎发生的独立预测因素。结论：IL-1B（rs 1143627）TT基因型和术前EIM是UC患者IPAA后结肠袋炎发生的统计学显著预测因素。
Background: Major complications in patients with ulcerative colitis (UC) include UC-associated cancer (UCAC) and postoperative pouchitis. We aimed to identify SNPs associated with UCAC/high-grade dysplasia (HGD) and pouchitis. Methods: Patients with UC who underwent ileal pouch-anal anastomosis (IPAA) with >2 years of follow-up after functioning pouches were included. Pouchoscopies were performed at least once to diagnose pouchitis according to the modified pouchitis disease activity index. SNP genotyping was performed for 8 SNPs reportedly associated with UCAC and pouchitis, namely: ELF1 (rs7329174), FCGR2A, (rs1801274), interleukin-1 beta (IL-1B; rs1143627), ITLN1 (rs2274910), MHC (rs7765379), TNF alpha (rs1799964), TNFSF15 (rs3810936), and UHMK1 (rs768910), using TaqMan genotyping technologies. We investigated the association of these SNPs with UCAC/HGD and pouchitis. Patients' background data were retrospectively collected, including the presence of preoperative extraintestinal manifestation (EIM). Results: A total of 91 Japanese patients with UC were included. None of the 8 SNPs were associated with UCAC/HGD in our cohort. Multivariable analyses proved that the presence of preoperative EIM (hazard ratio [HR] 3.313, 95% CI 1.325-8.289) and IL-1B (rs1143627) TT genotype (HR 2.425, 95% CI 1.049-5.61) were independent predictive factors for the development of overall pouchitis. The presence of preoperative EIM (HR 3.977, 95% CI 1.292-12.24) and IL-1B (rs1143627 TT genotype; HR 3.382, 95% CI 1.101-10.39) were also independent predictive factors for the development of chronic pouchitis. Conclusions: The IL-1B (rs1143627) TT genotype and preoperative EIM were statistically significant predictors of pouchitis development after IPAA in patients with UC.