补铁可能降低阿尔茨海默病的风险:孟德尔随机化研究  

Iron supplementation May Reduce the Risk of Alzheimer's Disease:A Mendelian Randomization Study

作　　者：陈家淇 田思予 李楠霖 管仟秋 游若澜 李雪萍[2] Chen Jiaqi;Tian Siyu;Li Nanlin;Guan Qianqiu;You Ruolan;Li Xueping(School of Clinical Medicine,Chengdu University of Traditional Chinese Medicine,Chengdu 610075,China;Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610032,China)

机构地区：[1]成都中医药大学临床医学院,成都610075 [2]成都中医药大学附属医院,成都610032

出　　处：《成都医学院学报》2024年第3期460-466,共7页Journal of Chengdu Medical College

基　　金：四川省干部保健科研项目(No:川干研2024-505)。

摘　　要：目的 采用两样本孟德尔随机化(MR)方法,探究血清铁状态与阿尔茨海默病(AD)的双向因果关联。方法 从公开的IEU Open GWAS数据库中获得血清铁、铁蛋白、转铁蛋白、转铁蛋白饱和度(n=23 986)及AD(n=407 089)的全基因组关联分析汇总数据。根据预设条件筛选出与暴露因素强相关的单核苷酸多态性作为工具变量,主要采用逆方差加权法进行双向MR分析,并进行异质性检验、水平多效性分析、敏感性分析,判断结果的稳定性和可靠性。采用多变量MR分析对可能与结局有因果关系的变量进一步研究,以确保该暴露因素对结局的独立影响。结果 单变量MR分析结果显示,血清铁(OR=0.952,95%CI:0.917~0.988,P=0.010)和转铁蛋白饱和度(OR=0.969,95%CI:0.944~0.995,P=0.018)与AD存在负向因果关联;用多变量MR分析校正了3个混杂因素(吸烟、受教育程度、体重指数)后,结果一致,相对稳定。研究结果均未发现异质性和多效性。结论 血清铁和转铁蛋白饱和度水平降低,可能增加AD的患病风险。Objective To explore the bidirectional causal relationship between serum iron status and Alzheimer's disease(AD)by using two-sample Mendelian randomization(MR)method.Methods Summary statistics related to serum iron,ferritin,transferrin,transferrin saturation(n=23986)and AD(n=407089)were obtained from IEU Open GWAS project,which was a publicly available genome-wide association analysis database.The single nucleotide polymorphisms that were strongly associated with the exposure factors were selected as instrumental variables according to the preset conditions.Inverse variance weighted was applied as the primary analytic method for bidirectional MR analyses.A series of analyses,including heterogeneity test,pleiotropy analysis and sensitivity analysis were also conducted to evaluate the stability and reliability of the results.Multivariate MR analysis was further performed on variables that might have a causal relationship with the outcome,in order to confirm the independent impact of the exposure factor on the outcome.Results The results of univariable MR analyses showed that serum iron(OR=0.952,95%Cl:0.917-0.988,P=0.010)as well as transferrin saturation(OR=0.969,95%C1:0.944-0.995,P=0.018)had negative causal effect on AD.After adjusting for three confounders,including smoking,education level and body mass index(BMI)by multivariate MR analyses,the causality between AD and serum iron status was still consistent and relatively stable.The research findings were not affected by heterogeneity or pleiotropy.Conclusion The reduction of serum iron and transferrin saturation levels are associated with an increased risk of AD.

关 键 词：铁状态 阿尔茨海默病 孟德尔随机化 

分 类 号：R749.16[医药卫生—神经病学与精神病学]