血清代谢物与溃疡性结肠炎的因果关系:一项两样本孟德尔随机化研究  

Causality of serum metabolites on ulcerative colitis:a two-sample Mendelian randomization study

作　　者：马芸 吉星宇 窦丹 王澍青 刘晏祯 张声生[2] 赵鲁卿[2] Ma Yun;Ji Xingyu;Dou Dan;Wang Shuqing;Liu Yanzhen;Zhang Shengsheng;Zhao Luqing(Beijing University of Chinese Medicine,Beijing 100029,China;Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,Beijing 100010,China)

机构地区：[1]北京中医药大学,北京100029 [2]首都医科大学附属北京中医医院消化中心,北京100010

出　　处：《中华临床营养杂志》2025年第1期31-39,共9页Chinese Journal of Clinical Nutrition

基　　金：北京市科技计划-首都临床特色诊疗技术研究及转化应用项目(Z221100007422094);首都医科大学优秀青年人才项目(B2308);国家自然科学基金重点专项(82341235);国家自然科学基金面上项目(81973764)。

摘　　要：目的评估血清代谢物对溃疡性结肠炎(ulcerative colitis,UC)的影响及因果关系,从而为本病患者的营养方案提供参考。方法采用两样本孟德尔随机化(Mendelian randomization,MR)分析,预测血清中代谢物与UC的因果关系。采用全基因组关联分析(genome-wide association studies,GWAS)对1400种代谢产物进行评估。其中,代谢产物作为暴露因素,UC作为结局。主要以逆方差加权法(inverse-variance weighted,IVW)进行因果推断,其他4种建模假设(MR-Egger回归、简单模型、加权中位数和加权模型)的MR方法用作额外分析,以提高结果的稳定性。通过异质性和多效性检验对结果进行验证,并对可能存在因果关系的代谢物进行代谢途径分析。结果MR分析显示,85种代谢物与UC可能存在因果关系,其中1,2-二棕榈酰甘油磷酸胆碱(P=2.75×10^(-6))和异戊酰基肉碱(P=1.84×10^(-5))与UC的发生显著相关。代谢途径分析确定了以上代谢物可能影响的5种代谢途径(P均<0.05),其中卟啉代谢途径(P=0.004)、嘧啶代谢途径(P=0.008)影响UC的可信度较高。结论部分血清代谢产物与UC发病风险存在因果关系,其中1,2-二棕榈酰甘油磷酸胆碱和异戊酰基肉碱水平的升高可能增加UC发病风险。卟啉代谢途径、嘧啶代谢途径等代谢途径可影响UC。Objective To evaluate the effect and causality of serum metabolites on the pathogenesis of ulcerative colitis(UC),so as to provide reference for nutritional programs for patients with UC.MethodsTwo-sample Mendelian randomization(MR)analysis was performed to estimate the causal relationship between serum metabolites and UC.Genome-wide association studies(GWAS)of 1400 metabolites were performed,with the metabolites as exposure and UC as outcome.Inverse-variance weighted(IVW)was used to calculate causal estimates.Four other MR methods with different modeling assumptions including MR-Egger,weighted median,weighted mode,and simple mode were used as additional analyses to improve the stability of the results.The results were validated through heterogeneity and pleiotropy tests.Finally,the possible causal metabolites were analyzed by metabolic pathway analysis.ResultsMR analysis revealed that 85 metabolites had a possible causal relationship with UC.Among them,phosphatidylglycerol 1,2-dipalmitoyl-gpc(DPPC)(P=2.75×10^(-6))and isovaleryl carnitine(C5)(P=1.84×10^(-5))were significant risk factors for UC.Metabolic pathway analysis identified 5 metabolic pathways that might be affected by these metabolites(all P<0.05),among which the porphyrin(P=0.004)and pyrimidine metabolic pathways(P=0.008)had higher confidence in impacting UC.ConclusionsThere are causal relationships between some serum metabolites(in particular 1,2-dipalmitoyl-GPC and isovalerylcarnitine)and the risk of UC.The porphyrin and pyrimidine metabolic pathways may impact the pathogenesis of UC.

关 键 词：溃疡性结肠炎 孟德尔随机化 血液代谢物 基因测定代谢产物 

分 类 号：R574.62[医药卫生—消化系统]