Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, 510623, Guangdong, China.
BMC Med Genomics. 2021 Jan 19;14(1):21. doi: 10.1186/s12920-020-00867-x.
Hirschsprung disease (HSCR) is a hereditary defect, which is characterized by the absence of enteric ganglia and is frequently concurrent with Hirschsprung-associated enterocolitis (HAEC). However, the pathogenesis for HSCR is complicated and remains unclear. Recent studies have shown that pro-inflammatory cytokines such as interleukin-11 (IL-11) are involved in the enteric nervous system's progress. It was found that IL-11 SNPs (rs8104023 and rs4252546) are associated with HSCR in the Korean population waiting for replication in an independent cohort. This study evaluated the relationship between IL-11 and the susceptibility of patients to HSCR by performing subphenotype interaction examination, HAEC pre-/post-surgical patient-only association analysis, and independence testing.
In this study, a cohort consisting of children from Southern China, comprising 1470 cases and 1473 controls, was chosen to examine the relationship between two polymorphisms (rs8104023 and rs4252546 in IL-11) and susceptibility to HSCR by replication research, subphenotype association analysis, and independence testing.
The results showed that IL-11 gene polymorphisms (rs8104023 and rs4252546) are not associated with the risk of HSCR in the Chinese population. The results of both short-segment and long-segment (S-HSCR and L-HSCR) surgery (3.34 ≤ OR ≤ 4.05, 0.02 ≤ P ≤ 0.04) showed that single nucleotide polymorphisms (SNP) rs8104023 is associated with susceptibility to HAEC.
This study explored the relationship between genetic polymorphisms and susceptibility to HAEC in HSCR subtypes for the first time. These findings should be replicated in a larger and multicentre study.
先天性巨结肠（HSCR）是一种遗传性缺陷，其特征为肠神经节缺失，常并发先天性巨结肠相关性肠炎（HAEC）。然而，HSCR 的发病机制较为复杂，目前尚不清楚。最近的研究表明，促炎细胞因子如白细胞介素-11（IL-11）参与肠神经系统的进展。研究发现，IL-11 SNP（rs8104023 和 rs4252546）与韩国等待在独立队列中复制的 HSCR 有关。本研究通过亚表型相互作用检验、HAEC 术前/术后患者相关性分析和独立性检验，评估了 IL-11 与 HSCR 患者易感性的关系。
本研究选择来自中国南方的儿童队列，包括 1470 例病例和 1473 例对照，通过复制研究、亚表型关联分析和独立性检验，检验 IL-11 中两个多态性（rs8104023 和 rs4252546）与 HSCR 易感性的关系。
结果表明，IL-11 基因多态性（rs8104023 和 rs4252546）与中国人群 HSCR 的发病风险无关。短段和长段（S-HSCR 和 L-HSCR）手术的结果（3.34≤OR≤4.05，0.02≤P≤0.04）表明，单核苷酸多态性（SNP）rs8104023 与 HAEC 的易感性相关。
本研究首次探讨了 HSCR 亚型中遗传多态性与 HAEC 易感性的关系。这些发现应在更大的多中心研究中进行复制。
