ABSTRACT

Objective: Inflammatory bowel disease (IBD) is a heterogeneous complex disease referring to two chronic disorders: Crohn’s disease (CD) and ulcerative colitis (UC). To clarify the relationship between IL-12B gene polymorphisms and susceptibility to CD and UC, a meta-analysis was conducted.

Methods: A comprehensive search of the PubMed, Web of Science, Embase and Cochrane databases was conducted up to Oct 2019. Studies evaluating the relationship between risk of IBD and variants of IL-12B (rs6887695, rs3212227 and rs10045431) were included. Odds ratio (OR) and 95% confidence interval (CI) were calculated. Trial sequential analysis (TSA) was implemented to estimate the required information size (RIS) and evaluate the credibility of the meta-analysis results.

Results: Seventeen studies containing 9827 patients with CD, 7583 patients with UC and 16044 controls were included. The results showed significant association between rs6887695 polymorphism and susceptibility to CD (allele model: OR = 1.17, 95% CI: 1.12–1.22) and UC (allele model: OR = 1.16, 95% CI: 1.09–1.23), and “C” allele carriers had a higher risk, with TSA conclusive. For rs10045431, no significant association with CD susceptibility was identified, while a significantly increased risk in UC was found (allele mode: OR = 1.16, 95% CI: 1.07–1.25), both results were conclusive according to TSA. No significant association between rs3212227 and CD or UC susceptibility was found, and TSA research warranted further investigation to certify the results. No significant heterogeneity was found.

Conclusion: IL-12B rs6887695 polymorphism was associated with increased risk of CD and UC, while IL-12B rs10045431 polymorphism might only be correlated with the risk of UC.

Abbreviations: IBD: inflammatory bowel disease; CD: Crohn’s disease; UC: ulcerative colitis; IL-12B: interleukin-12B; OR: odds ratio; CI: confidence interval; TSA: trial sequential analysis; RIS: required information size; DCs: dendritic cells; NK: nature killer; APCs: antigen-presenting cells; TNF: tumor necrosis factor; SNP: single nucleotide polymorphisms; HWE: Hardy–Weinberg equilibrium; NOS: Newcastle–Ottawa scale; RRR: relative risk reduction

摘要

目的：炎症性肠病（IBD）是一种异质性复杂疾病，涉及两种慢性疾病：克罗恩病（CD）和溃疡性结肠炎（UC）。为了阐明 IL-12B 基因多态性与 CD 和 UC 易感性之间的关系，进行了荟萃分析。

方法：截至 2019 年 10 月，对 PubMed、Web of Science、Embase 和 Cochrane 数据库进行了全面搜索。包括评估 IBD 风险与 IL-12B 变体（rs6887695、rs3212227 和 rs10045431）之间关系的研究。计算优势比 (OR) 和 95% 置信区间 (CI)。实施试验序贯分析（TSA）以估计所需信息量（RIS）并评估荟萃分析结果的可信度。

结果：共纳入 17 项研究，包括 9827 名 CD 患者、7583 名 UC 患者和 16044 名对照。结果显示 rs6887695 多态性与 CD 易感性（等位基因模型：OR = 1.17，95% CI：1.12-1.22）和 UC（等位基因模型：OR = 1.16，95% CI：1.09-1.23）和“C ”等位基因携带者的风险更高，TSA 是决定性的。对于 rs10045431，未发现与 CD 易感性显着相关，而发现 UC 风险显着增加（等位基因模式：OR = 1.16，95% CI：1.07-1.25），根据 TSA，这两个结果都是结论性的。未发现 rs3212227 与 CD 或 UC 易感性之间存在显着关联，TSA 研究需要进一步调查以证明结果。未发现显着异质性。

结论：IL-12B rs6887695多态性与CD和UC风险增加相关，而IL-12B rs10045431多态性可能仅与UC风险相关。

缩写：IBD：炎症性肠病；CD：克罗恩病；UC：溃疡性结肠炎；IL-12B：白细胞介素-12B；或：优势比；CI：置信区间；TSA：试验序贯分析；RIS：所需信息量；DCs：树突状细胞；NK：自然杀手；APCs：抗原呈递细胞；TNF：肿瘤坏死因子；SNP：单核苷酸多态性；HWE：哈代-温伯格均衡；NOS：纽卡斯尔-渥太华量表；RRR：相对风险降低