Xiao Ze-Fa, Chai Wei-Hao, Shu Xiao-Long, Yuan Hong-Rui, Guo Fei
The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
Department of Graduate School, Xinjiang Medical University, Urumqi, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr;398(4):3817-3827. doi: 10.1007/s00210-024-03493-x. Epub 2024 Oct 3.
Cholecystitis, characterized by inflammation of the gallbladder, is intricately linked to immune cells and the cytokines they produce. Despite this association, the specific contributions of immune cells to the onset and progression of cholecystitis remain to be fully understood. To delineate this relationship, we utilized the Mendelian randomization (MR) method to scrutinize the causal connections between 731 immune cell phenotypes and cholecystitis. By conducting MR analysis on 731 immune cell markers from public datasets, this study seeks to understand their potential impact on the risk of cholecystitis. It aims to elucidate the interactions between immune phenotypes and the disease, aiming to lay the groundwork for advancing precision medicine and developing effective treatment strategies for cholecystitis. Taking immune cell phenotypes as the exposure factor and cholecystitis as the outcome event, this study used single nucleotide polymorphisms (SNPs) closely associated with both immune cell phenotypes and cholecystitis as genetic instrumental variables. We conducted a two-sample MR analysis on genome-wide association studies (GWAS) data. Our research thoroughly examined 731 immune cell markers, to determine potential causal relationships with susceptibility to cholecystitis. Sensitivity analyses were performed to ensure the robustness of our findings, excluding the potential impacts of heterogeneity and pleiotropy. To avoid reverse causality, we conducted reverse MR analyses with cholecystitis as the exposure factor and immune cell phenotypes as the outcome event. Among the 731 immune phenotypes, our study identified 21 phenotypes with a causal relationship to cholecystitis (P < 0.05). Of these, eight immune phenotypes exhibited a protective effect against cholecystitis (odds ratio (OR) < 1), while the other 13 immune phenotypes were associated with an increased risk of developing cholecystitis (OR > 1). Additionally, employing the false discovery rate (FDR) method at a significance level of 0.2, no significant causal relationship was found between cholecystitis and immune phenotypes. Our research has uncovered a significant causal relationship between immune cell phenotypes and cholecystitis. This discovery not only enhances our understanding of the role of immune cells in the onset and progression of cholecystitis but also establishes a foundation for developing more precise biomarkers and targeted therapeutic strategies. It provides a scientific basis for more effective and personalized treatments in the future. These findings are expected to substantially improve the quality of life for patients with cholecystitis and mitigate the impact of the disease on patients and their families.
胆囊炎以胆囊炎症为特征,与免疫细胞及其产生的细胞因子密切相关。尽管存在这种关联,但免疫细胞对胆囊炎发病和进展的具体作用仍有待充分了解。为了阐明这种关系,我们利用孟德尔随机化(MR)方法来研究731种免疫细胞表型与胆囊炎之间的因果联系。通过对来自公共数据集的731种免疫细胞标志物进行MR分析,本研究旨在了解它们对胆囊炎风险的潜在影响。其目的是阐明免疫表型与该疾病之间的相互作用,旨在为推进精准医学和制定有效的胆囊炎治疗策略奠定基础。本研究以免疫细胞表型为暴露因素,以胆囊炎为结局事件,使用与免疫细胞表型和胆囊炎均密切相关的单核苷酸多态性(SNP)作为遗传工具变量。我们对全基因组关联研究(GWAS)数据进行了两样本MR分析。我们的研究全面检查了731种免疫细胞标志物,以确定与胆囊炎易感性的潜在因果关系。进行了敏感性分析以确保我们研究结果的稳健性,排除了异质性和多效性的潜在影响。为避免反向因果关系,我们以胆囊炎为暴露因素、免疫细胞表型为结局事件进行了反向MR分析。在731种免疫表型中,我们的研究确定了21种与胆囊炎存在因果关系的表型(P<0.05)。其中,8种免疫表型对胆囊炎具有保护作用(比值比(OR)<1),而其他13种免疫表型与患胆囊炎风险增加相关(OR>1)。此外,在显著性水平为0.2时采用错误发现率(FDR)方法,未发现胆囊炎与免疫表型之间存在显著因果关系。我们的研究发现了免疫细胞表型与胆囊炎之间存在显著因果关系。这一发现不仅增强了我们对免疫细胞在胆囊炎发病和进展中作用的理解,还为开发更精确的生物标志物和靶向治疗策略奠定了基础。它为未来更有效和个性化的治疗提供了科学依据。这些发现有望大幅提高胆囊炎患者的生活质量,并减轻该疾病对患者及其家庭的影响。