PCSK9抑制剂与自身免疫性疾病之间的关联:孟德尔随机化研究
Association Between PCSK9 Inhibitors and Autoimmune Diseases:A Mendelian Randomization Study
李沁瑶 1胥崟崧1
作者信息
- 1. 成都中医药大学,四川成都 610075
- 折叠
摘要
目的 观察性研究表明,PCSK9抑制剂与自身免疫性疾病之间可能存在关联.但是,从观察性研究中推断因果关系会受到残余混杂效应、反向因果关系和偏倚的影响.笔者进行两样本孟德尔随机化(Mendelian randomization,MR)分析,以评估PCSK9抑制剂对自身免疫性疾病(克罗恩病,银屑病,类风湿性关节炎,系统性红斑狼疮,1型糖尿病,溃疡性结肠炎)的潜在因果关系.方法 选取与低密度脂蛋白相关的药物靶基因内部或附近的遗传变异(单核苷酸多态性)作为工具变量,应用MR方法对欧洲血统的全基因组关联研究的数据进行分析.逆方差加权(Inverse-variance weighted,IVW)MR方法作为主要分析方法,进行敏感性分析以检测结果的稳健性.结果 IVW-MR分析观察到PCSK9介导的低密度脂蛋白胆固醇与银屑病(OR=1.264,95％CI=1.117～1.431;P＜0.01)、类风湿性关节炎(OR=1.151,95％CI=1.032～1.284;P=0.011)、系统性红斑狼疮(OR=1.740,95％CI=1.227～2.468;P＜0.01)之间存在正相关.结论 MR分析支持PCSK9抑制剂对银屑病、类风湿性关节炎和系统性红斑狼疮的可能治疗作用.
Abstract
OBJECTIVE Several observational studies suggest a possible link between PCSK9 inhibitors and autoimmune diseases.However,inferring causality from these studies can be influenced by residual confounding effects,reverse causation,and bias.To investigate the potential causal effect of proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitors on autoimmune disease(Crohn's disease,Psoriasis,Rheumatoid arthritis,Systemic lupus erythematosus,Type 1 Diabetes and Ulcerative colitis),we performed a Mendelian randomization(MR)-based study.METHODS Selecting genetic variants(single nucleotide polymorphisms)near or within drug target genes associated with low-density lipoprotein as instrumental variables,and applying MR methods to analyze data from genome-wide association studies of European ancestry.The inverse-variance weighted(IVW)-MR approach was used as the main analysis method to conduct sensitivity analysis and test the robustness of the results.RESULTS The IVW-MR analysis revealed significant evidence for an association between PCSK9-mediated LDL-C and the risk of psoriasis(OR=1.264,95％CI=1.117-1.431,P＜0.01),rheumatoid arthritis(OR=1.151,95％CI=1.032-1.284,P=0.011),systemic lupus erythematosus(OR=1.740,95％CI=1.227-2.468,P＜0.01).CONCLUSION Our findings support a potential therapeutic effect of PCSK9 inhibitors on psoriasis,rheumatoid arthritis and systemic lupus erythematosus.
关键词
PCSK9抑制剂/自身免疫性疾病/孟德尔随机化Key words
PCSK9 inhibitors/autoimmune disease/mendelian randomization引用本文复制引用
出版年
2024
NETL
NSTL
万方数据