基于血浆代谢组学探究神经酰胺与盐敏感性高血压的因果关联  

Causal association between ceramide and salt sensitive hypertension based on plasma metabolomics

作　　者：杨晓俊 张博闻 李博雅 温馥源 屈艾彬 姚昕玥 张玲[1] YANG Xiaojun;ZHANG Bowen;LI Boya;WEN Fuyuan;QU Aibin;YAO Xinyue;ZHANG Ling(School of Public Health,Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学公共卫生学院,北京100069

出　　处：《医学新知》2025年第4期367-375,共9页New Medicine

基　　金：国家自然科学基金面上项目(82273708)。

摘　　要：目的通过关联分析和孟德尔随机化(Mendelian randomization,MR)分析,探究血浆代谢物与盐敏感性高血压(salt sensitive hypertension,SSH)之间的关联及因果关系。方法基于血压盐敏感性系统流行病学队列基线调查数据,选取60例研究对象进行非靶向代谢组学和全基因组检测。采用多因素Logistic回归分析血浆代谢物与SSH之间的关联。通过单样本和两样本MR分析评估差异代谢物与SSH之间的因果关系并进行敏感性分析。结果共检测出970种代谢物,其中73种与SSH之间的关联存在统计学意义(P<0.05)。FDR校正后,神经酰胺Cer(d34:0)[OR=1.55,95%CI(1.36,1.76)]和Cer(d40:1)[OR=2.19,95%CI(1.66,2.91)]与SSH仍呈显著正相关。单样本MR分析结果显示,Cer(d40:1)的简单遗传风险评分(genetic risk score,GRS)[OR=2.470,95%CI(1.887,3.234)]和加权GRS[OR=3.362,95%CI(1.303,8.674)]均与SSH存在因果关系。两样本MR分析未发现Cer(d34:0)和Cer(d40:1)与SSH之间存在因果关系(P>0.05)。结论本研究发现血浆代谢物神经酰胺Cer(d34:0)和Cer(d40:1)是SSH的危险因素,MR结果进一步支持Cer(d40:1)与SSH之间存在因果关系,为SSH的早期筛查和病因学研究提供新的证据。Objective To investigate the association and causal relationship between plasma metabolites and salt sensitive hypertension(SSH)using association analysis and Mendelian randomization(MR).Methods Based on the baseline survey data from the System Epidemiology Study on Salt Sensitivity of Blood Pressure(EpiSS),60 participants were selected for untargeted metabolomics and whole-genome genotyping.Multivariable Logistic regression analysis was conducted to explore the association between plasma metabolites and SSH.One-sample and twosample MR analyses and sensitivity analysis were performed to assess the causal relationship between metabolites and SSH.Results A total of 970 metabolites were measured,73 of which showed a statistically significant association with SSH(P<0.05).After false discovery rate(FDR)correction,ceramide Cer(d34:0)and Cer(d40:1)remained significantly positively associated with SSH,with OR(95%CI)of 1.55(1.36,1.76)and 2.19(1.66,2.91),respectively.The one-sample MR analysis revealed a causal relationship between Cer(d40:1)and SSH,with both simple genetic risk score(GRS)[OR=2.470,95%CI(1.887,3.234)]and weighted GRS[OR=3.362,95%CI(1.303,8.674)].Two-sample MR analysis did not find a causal relationship between Cer(d34:0)and Cer(d40:1)and SSH(P>0.05).Conclusion This study identified plasma metabolites Cer(d34:0)and Cer(d40:1)as potential risk factors for SSH,with MR results further supporting a causal relationship between Cer(d40:1)and SSH.These findings provide new evidence for early screening and etiological research of SSH.

关 键 词：血浆代谢物 盐敏感性高血压 代谢组学 孟德尔随机化 

分 类 号：R544.1[医药卫生—心血管疾病]