血液代谢物与原发性硬化性胆管炎风险关系:一项双样本孟德尔随机化研究  

Association of blood metabolites with primary sclerosing cholangitis risk:a two-sample Mendelian randomized study

作　　者：汪增秀[1] 吴卫锋 WANG Zeng-xiu;WU Wei-feng(Department of Hepatology,the Second Hospital of Nanjing,Nanjing University of Chinese Medicine,Jiangsu 210000,China)

机构地区：[1]南京中医药大学附属南京医院(南京市第二医院)肝病一科,江苏210003

出　　处：《肝脏》2024年第11期1401-1404,共4页Chinese Hepatology

摘　　要：目的运用孟德尔随机化分析血液代谢物和原发性硬化性胆管炎之间的关联。方法获取PSC和血液代谢物的相关全基因组关联研究(GWAS)数据,筛选其中的单核苷酸多态性(SNP)作为工具变量,采用逆方差加权法、加权中位数法、MR-Egger回归法和加权模式法进行两样本孟德尔随机化(MR)分析。结果基于逆方差加权法分析甘露醇(P=0.049)、尿素(P=0.035)、亚油酸酯(18:2n6)(P=0.049)、咖啡因(P=0.039)、亮氨酸(P=0.019)的水平与PSC的风险呈现正相关,而左旋肉碱(P=0.049)、维生素C(P=0.017)、维生素B5(P=0.005)、棕榈酸酯(16:0)(P=0.030)、肌酸酐(P=0.043)与PSC的风险负相关。结论11种代谢物可能与原发性硬化性胆管炎存在因果关联,其中6种的关联性更加可靠,可为探索原发性硬化性胆管炎的发病机制及早期筛检和治疗提供参考。Objective To investigate the association between blood metabolite levels and the risk of primary sclerosing cholangitis(PSC)using Mendelian randomization.Methods Genome-wide association study(GWAS)data for PSC and blood metabolites were obtained.Single nucleotide polymorphisms(SNPs)were selected as instrumental variables,and two-sample Mendelian randomization(MR)analyses were conducted using inverse variance weighting,the weighted median method,and MR-Egger regression.Results Higher levels of mannitol(P=0.049),urea(P=0.035),linoleate(18:2n6)(P=0.049),caffeine(P=0.039),and leucine(P=0.019)were positively associated with an increased risk of PSC.In contrast,elevated levels of L-carnitine(P=0.049),vitamin C(P=0.017),pantothenate(P=0.005),palmitate(16:0)(P=0.030),and creatinine(P=0.043)were negatively associated PSC risk.Conclusion Eleven metabolites may have causal associations with chronic kidney disease,offering potential insights for understanding its pathogenesis and aiding in early screening and therapeutic strategies.

关 键 词：血液代谢物 孟德尔随机化 相关性研究 原发性硬化性胆管炎 

分 类 号：R575.7[医药卫生—消化系统]