A Polymorphism in Interleukin-1β Gene Is Associated with the Development of Pouchitis in Japanese Patients with Ulcerative Colitis

Abstract

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-1β (IL-1B; rs1143627), ITLN1 (rs2274910), MHC (rs7765379), TNFα (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.

Keywords: Interleukin-1β; Pouchitis; Single nucleotide polymorphism.