[1]戎义发,姜凯,贾海峰,等.炎症因子与强直性脊柱炎及血液代谢物因果关系的孟德尔随机化分析[J].中医正骨,2024,36(11):26-41.
　RONG Yifa,JIANG Kai,JIA Haifeng,et al.The causal relationships of inflammatory factors with ankylosing spondylitis and blood metabolites:a mendelian randomization analysis[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2024,36(11):26-41.
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炎症因子与强直性脊柱炎及血液代谢物因果关系的孟德尔随机化分析()
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《中医正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第36卷
期数:
2024年11期
页码:
26-41
栏目:
数据库研究
出版日期:
2024-11-20

文章信息/Info

Title:
The causal relationships of inflammatory factors with ankylosing spondylitis and blood metabolites:a mendelian randomization analysis
作者:
戎义发1; 姜凯1; 贾海峰1; 李翰政1; 李树栋1; 李刚2
1.山东中医药大学第一临床医学院,山东 济南 250014; 2.山东中医药大学附属医院,山东 济南 250014
Author(s):
RONG Yifa1; JIANG Kai1; JIA Haifeng1; LI Hanzheng1; LI Shudong1; LI Gang2
1.The First Clinical Medical College of Shandong University of Traditional Chinese Medicine,Jinan 250014,Shandong,China 2.The Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250014,Shandong,China
关键词:
脊柱炎; 强直性;  炎症介导素类;  代谢物;  孟德尔随机化分析
Keywords:
spondylitis; ankylosing;  inflammation mediators;  metabolites;  Mendelian randomization analysis
摘要:
目的:探讨炎症因子与强直性脊柱炎(ankylosing spondylitis,AS)及血液代谢物的因果关系。方法:从全基因组关联研究(genome-wide association study,GWAS)Catalog数据库中获取炎症因子表达水平和血液代谢物指标(代谢物水平或代谢物比率)的GWAS数据,从FinnGen数据库中获取AS的GWAS数据。基于工具变量筛选标准,筛选符合要求的炎症因子表达水平的单核苷酸多态性(single nucleotide polymorphism,SNP)位点。将筛选出的炎症因子表达水平的SNP位点作为工具变量,以AS为结局进行孟德尔随机化(Mendelian randomization,MR)分析,并进行敏感性分析; 将确定的与AS具有可靠因果关系的炎症因子表达水平的SNP位点作为工具变量,以血液代谢物指标为结局进行MR分析,并进行敏感性分析。结果:①炎症因子表达水平与AS的因果关系分析结果。CD244、成纤维细胞生长因子(fibroblast growth factor,FGF)-23、FMS样酪氨酸激酶3配体(FMS-like tyrosine kinase 3 ligand,FIt3L)、白细胞介素(interleukin,IL)-7表达水平与AS存在可靠的因果关系,其中CD244、FIt3L表达水平与AS呈负相关,FGF-23、IL-7表达水平与AS呈正相关。②炎症因子表达水平与血液代谢物指标的因果关系分析结果。CD244、FGF-23、FIt3L、IL-7表达水平分别与61项、62项、37项、68项血液代谢物指标存在可靠的因果关系。结论:FGF-23、IL-7、CD244、FIt3L表达水平与AS存在可靠的因果关系,这4种炎症因子表达水平分别与多项血液代谢物指标存在可靠的因果关系; 这为探索AS的发生机制和治疗AS的药物靶点提供了参考。
Abstract:
Objective:To explore the causal relationships of inflammatory factors with ankylosing spondylitis(AS)and blood metabolites.Methods:The genome-wide association study(GWAS)data about the expression levels of inflammatory factors and blood metabolite indicators(metabolite levels or metabolite ratios)were retrieved and extracted from the GWAS Catalog database,and that about AS from the FinnGen database.According to the instrumental variable screening criteria,the eligible single nucleotide polymorphism(SNP)loci for the expression levels of inflammatory factors were screened as the instrumental variable,and then a mendelian randomization(MR)analysis was conducted with AS as the outcome variable to assess the causality between the expression levels of inflammatory factors and AS,and the sensitivity was examined.Furthermore,another MR analysis was conducted by taking the SNP loci of the expression levels of inflammatory factor having a reliable causality with AS as the instrumental variable,and the blood metabolite indicators as the outcome variable to assess the causality between the expression levels of inflammatory factors and blood metabolite indicators,and the sensitivity was examined.Results:①The causality between the expression levels of inflammatory factors and AS.The expression levels of CD244,fibroblast growth factor(FGF)-23,FMS-like tyrosine kinase 3 ligand(FIt3L)and interleukin(IL)-7 exhibited a reliable causal relationship with AS,among which,the expression levels of CD244 and FIt3L showed a inverse causal relationship with AS,while the expression levels of FGF-23 and IL-7 presented a positive causal relationship with AS.②The causality between the expression levels of inflammatory factors and blood metabolite indicators.The expression levels of CD244,FGF-23,FIt3L and IL-7 exhibited a reliable causal relationship with 61,62,37 and 68 blood metabolite indicators,respectively.Conclusion:The expression levels of FGF-23,IL-7,CD244 and FIt3L exhibit a reliable causal relationship with AS,and they also have a reliable causal relationship with multiterm blood metabolite indicators,respectively,which provides a reference for exploring the pathogenesis of AS and the potential drug targets in treating AS.

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更新日期/Last Update: 1900-01-01