Zhang Cong, Fan Xiujing, Li Zhijun, Hu Zongyi, He Chengcheng, Wang Shanping, Li Mingsong
Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Department of Gastroenterology, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Department of Gastroenterology, The First People's Hospital of Foshan, Foshan, China.
Front Genet. 2024 Aug 14;15:1324893. doi: 10.3389/fgene.2024.1324893. eCollection 2024.
Acute pancreatitis (AP) is an extraintestinal manifestation of inflammatory bowel disease (IBD). Numerous observational studies have reported an increased risk of AP in patients diagnosed with IBD. However, the causal association and directionality between IBD or its subtypes and the development of AP remains unclear due to the limitations of observational research. This study aims to explore the relationship between IBD or its subtypes and AP risk using Mendelian Randomization (MR) method.
A two-sample bidirectional MR study was conducted, selecting genetic variants associated with IBD and AP as instrumental variables from the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC) and FinnGen databases, respectively. The inverse-variance weighted (IVW) method used as the primary approach for causal inference. The Cochran Q test was employed for heterogeneity assessment. Sensitivity analyses were performed using the MR Egger intercept test, MR-Presso, and Leave-one-out method.
The results revealed that IBD (OR = 1.049, 95% CI = 1.010-1.090, = 0.013) and ulcerative colitis (UC) (OR = 1.057, 95% CI = 1.013-1.102, = 0.011) were significantly associated with an increased risk of AP. However, Crohn's disease (CD) (OR = 1.023, 95% CI = 0.993-1.055, = 0.134) did not show a causal association with the risk of AP. Interestingly, AP was suggestively associated with a decreased risk of CD (OR = 0.797, 95% CI = 0.637-0.997, = 0.047). Furthermore, there was no causal association between AP and the risk of IBD (OR = 0.886, 95% CI = 0.753-1.042, = 0.144) or UC (OR = 0.947, 95% CI = 0.773-1.159, = 0.595).
In conclusion, this study provides genetic evidence supporting the causal influence of IBD (specifically UC) on AP, while CD does not appear to have a causal impact on AP.
急性胰腺炎（AP）是炎症性肠病（IBD）的一种肠外表现。众多观察性研究报告称，被诊断为IBD的患者发生AP的风险增加。然而，由于观察性研究的局限性，IBD及其亚型与AP发生之间的因果关联和方向性仍不明确。本研究旨在使用孟德尔随机化（MR）方法探讨IBD及其亚型与AP风险之间的关系。
进行了一项两样本双向MR研究，分别从国际炎症性肠病遗传学联盟（IIBDGC）和芬兰基因数据库中选择与IBD和AP相关的基因变异作为工具变量。采用逆方差加权（IVW）方法作为因果推断的主要方法。使用Cochran Q检验进行异质性评估。使用MR Egger截距检验、MR-Presso和留一法进行敏感性分析。
结果显示，IBD（比值比[OR]=1.049，95%置信区间[CI]=1.010-1.090，P=0.013）和溃疡性结肠炎（UC）（OR=1.057，95%CI=1.013-1.102，P=0.011）与AP风险增加显著相关。然而，克罗恩病（CD）（OR=1.023，95%CI=0.993-1.055，P=0.134）与AP风险之间未显示出因果关联。有趣的是，AP与CD风险降低存在提示性关联（OR=0.797，95%CI=0.637-0.997，P=0.047）。此外，AP与IBD（OR=0.886，95%CI=0.753-1.042，P=0.144）或UC（OR=0.947，95%CI=0.773-1.159，P=0.595）风险之间不存在因果关联。
总之，本研究提供了遗传证据，支持IBD（特别是UC）对AP的因果影响，而CD似乎对AP没有因果影响。
