Peng Shayong, Wei Yongguang, Huang Huasheng, Lan Chenlu, Zeng Zhiming, Zhu Guangzhi, Peng Tao
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, P.R. China.
Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning, P.R. China.
Medicine (Baltimore). 2025 Mar 7;104(10):e41745. doi: 10.1097/MD.0000000000041745.
Asymptomatic gallbladder and biliary tract calculus may make into symptomatic disease or bring anxiety for patients. The formation of gallstones was associated with genetic risk factors and metabolic abnormalities. Genome-wide association studies (GWAS) data of 1400 plasma metabolites (PMs) and 91 circulating inflammatory cytokines (CICs) were obtained from the GWAS catalog, while the GWAS data of calculus of gallbladder without cholecystitis and calculus of bile duct without cholangitis or cholecystitis were retrieved from the IEU OpenGWAS project. The causalities from PMs or CICs to asymptomatic bile duct or cholecyst calculus were explored by 2-sample Mendelian randomization (MR) analysis. Furthermore, the MR analyses were implemented from the identified PMs to CICs. Following the false discovery rate adjustment, the significant causalities, including 6 CICs and 5 PMs on asymptomatic biliary stone and 5 CICs and 48 PMs on asymptomatic gallstone, were identified. Fibroblast growth factor 19 (FGF-19) and aspartate/mannose ratio were the common protective factors of asymptomatic biliary tract calculus, while Monocyte chemoattractant protein 2 (CCL-2) may serve as a disease-promoting agent. Moreover, Bilirubin degradation product, C17H18N2O4 (1) levels, and Bilirubin (Z,Z)/etiocholanolone glucuronide ratio were associated with FGF-19 level, while aspartate/mannose ratio was related to TNF-related apoptosis-inducing ligand level. Based on MR analysis, we identified the multiple PMs and CICs, especially FGF-19, which may affect the formation of gallbladder and biliary tract calculus. Moreover, the partial CICs could be the downstream mediator of PMs related to asymptomatic gallbladder and biliary tract calculus. These results contributed to supporting previous studies and provided evidence for disease prevention or management.
无症状胆囊和胆道结石可能会发展为有症状的疾病或给患者带来焦虑。胆结石的形成与遗传风险因素和代谢异常有关。从全基因组关联研究（GWAS）目录中获取了1400种血浆代谢物（PMs）和91种循环炎症细胞因子（CICs）的GWAS数据，而无胆囊炎的胆囊结石和无胆管炎或胆囊炎的胆管结石的GWAS数据则从IEU OpenGWAS项目中检索。通过两样本孟德尔随机化（MR）分析探讨了PMs或CICs与无症状胆管或胆囊结石之间的因果关系。此外，还从已鉴定的PMs到CICs进行了MR分析。经过错误发现率调整后，确定了显著的因果关系，包括6种CICs和5种PMs与无症状胆石症有关，5种CICs和48种PMs与无症状胆结石有关。成纤维细胞生长因子19（FGF-19）和天冬氨酸/甘露糖比值是无症状胆道结石的常见保护因素，而单核细胞趋化蛋白2（CCL-2）可能是一种促病因子。此外，胆红素降解产物C17H18N2O4（1）水平和胆红素（Z,Z）/表雄酮葡萄糖醛酸苷比值与FGF-19水平相关，而天冬氨酸/甘露糖比值与肿瘤坏死因子相关凋亡诱导配体水平相关。基于MR分析，我们确定了多种PMs和CICs，尤其是FGF-19，它们可能影响胆囊和胆道结石的形成。此外，部分CICs可能是与无症状胆囊和胆道结石相关的PMs的下游介质。这些结果有助于支持先前的研究，并为疾病预防或管理提供证据。
