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白细胞介素-12B基因多态性与炎症性肠病易感性:一项荟萃分析和序贯试验分析

The Polymorphisms of Interleukin-12B Gene and Susceptibility to Inflammatory Bowel Diseases: A Meta-analysis and Trial Sequential Analysis.

作者信息

Wang Jing, Liu Hong, Wang Yadan, Wu Jing, Wang Canghai, Liu Kuiliang, Qin Qin

机构信息

Department of Gastroenterology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.

Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

出版信息

Immunol Invest. 2021 Nov;50(8):987-1006. doi: 10.1080/08820139.2020.1863981. Epub 2021 Jan 4.

DOI:10.1080/08820139.2020.1863981
PMID:33390082
Abstract

: 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.: 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.: 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.: 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.: 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

炎症性肠病(IBD)是一种异质性复杂疾病,指两种慢性病症:克罗恩病(CD)和溃疡性结肠炎(UC)。为阐明白细胞介素12B(IL - 12B)基因多态性与CD和UC易感性之间的关系,进行了一项荟萃分析。

截至2019年10月,对PubMed、科学网、Embase和Cochrane数据库进行了全面检索。纳入评估IBD风险与IL - 12B变体(rs6887695、rs3212227和rs10045431)之间关系的研究。计算比值比(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。

纳入了17项研究,其中包括9827例CD患者、7583例UC患者和16044例对照。结果显示,rs6887,695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易感性(等位基因模型:OR = 1.16,95% CI:1.09 - 1.23)之间存在显著关联,“C”等位基因携带者风险更高,TSA结果具有决定性。对于rs10045431,未发现与CD易感性有显著关联,而发现其在UC中的风险显著增加(等位基因模型:OR = 1.16,95% CI:1.07 - 1.25),根据TSA这两个结果均具有决定性。未发现rs3212227与CD或UC易感性之间存在显著关联,TSA研究需要进一步调查以证实结果。未发现显著异质性。

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。

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;OR:比值比;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:自然杀伤细胞;APCs:抗原呈递细胞;TNF:肿瘤坏死因子;SNP:单核苷酸多态性;HWE:哈迪 - 温伯格平衡;NOS:纽卡斯尔 - 渥太华量表;RRR:相对风险降低

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