Department of Surgery, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, the Netherlands.
Department of Surgery, St Antonius Hospital, Nieuwegein, the Netherlands.
BJS Open. 2020 Feb;4(1):3-15. doi: 10.1002/bjs5.50231. Epub 2019 Dec 3.
Genetic risk factors can provide insight into susceptibility for acute pancreatitis (AP) and disease progression towards (infected) necrotizing pancreatitis and persistent organ failure. The aim of the study was to undertake a systematic review of the genetic evidence for AP.
Online databases (MEDLINE, Embase, BIOSIS, Web of Science, Cochrane Library) were searched to 8 February 2018. Studies that reported on genetic associations with AP susceptibility, severity and/or complications were eligible for inclusion. Meta-analyses were performed of variants that were reported by at least two data sources. Venice criteria and Bayesian false-discovery probability were applied to assess credibility.
Ninety-six studies reporting on 181 variants in 79 genes were identified. In agreement with previous meta-analyses, credible associations were established for SPINK1 (odds ratio (OR) 2·87, 95 per cent c.i. 1·89 to 4·34), IL1B (OR 1·23, 1·06 to 1·42) and IL6 (OR 1·64, 1·15 to 2·32) and disease risk. In addition, two novel credible single-nucleotide polymorphisms were identified in Asian populations: ALDH2 (OR 0·48, 0·36 to 0·64) and IL18 (OR 1·47, 1·18 to 1·82). Associations of variants in TNF, GSTP1 and CXCL8 genes with disease severity were identified, but were of low credibility.
Genetic risk factors in genes related to trypsin activation and innate immunity appear to be associated with susceptibility to and severity of AP.
遗传风险因素可以深入了解急性胰腺炎（AP）的易感性，以及向（感染性）坏死性胰腺炎和持续性器官衰竭发展的疾病进程。本研究的目的是系统综述 AP 的遗传证据。
在线数据库（MEDLINE、Embase、BIOSIS、Web of Science、Cochrane Library）进行搜索，截至 2018 年 2 月 8 日。有资格纳入的研究报告了与 AP 易感性、严重程度和/或并发症相关的遗传关联。对至少两个数据源报告的变异进行了荟萃分析。应用威尼斯标准和贝叶斯错误发现概率来评估可信度。
确定了 96 项研究，共报道了 79 个基因中的 181 个变异。与之前的荟萃分析一致，鉴定了可信的关联SPINK1（比值比（OR）2.87，95%置信区间[CI]1.89 至 4.34）、IL1B（OR 1.23，1.06 至 1.42）和 IL6（OR 1.64，1.15 至 2.32）与疾病风险。此外，还在亚洲人群中鉴定了两个新的可信单核苷酸多态性：ALDH2（OR 0.48，0.36 至 0.64）和 IL18（OR 1.47，1.18 至 1.82）。还发现 TNF、GSTP1 和 CXCL8 基因的变异与疾病严重程度相关，但可信度较低。
与胰蛋白酶激活和先天免疫相关的基因中的遗传风险因素似乎与 AP 的易感性和严重程度相关。
