摘要
背景:颈椎间盘退变是一种常见的退行性疾病,而炎症蛋白在颈椎间盘退变中起到重要作用,但其中的具体机制仍有待深入研究。目的:采用孟德尔随机化方法来评估91种炎症蛋白与颈椎间盘退变之间的潜在因果关系。方法:获取91种炎症蛋白的全基因组关联分析统计数据(从GCST90274758到GCST90274848)和芬兰数据库中颈椎间盘退变的全基因组关联分析数据(finngen_R10_M13_CERVICDISCV)。采用逆方差加权法、MR-Egger回归法、加权中位数法、加权模型法和简单模型法来研究炎症蛋白与颈椎间盘退变之间的因果关系。敏感性分析检验孟德尔随机化分析结果是否可靠,然后以同样方法进行反向孟德尔随机化分析。结果与结论:①正向分析结果表明,共有6种炎症蛋白与颈椎间盘退变有显著的因果关系,其中胶质细胞系源性神经营养因子水平(OR=1.095,95%CI:1.012-1.184,P=0.023)、白细胞介素4水平(OR=1.094,95%CI:1.002-1.194,P=0.045)和单核细胞趋化蛋白1水平(OR=1.062,95%CI:1.001-1.127,P=0.048)与颈椎间盘退变风险呈直接的正向因果关联;白细胞介素17 C水平(OR=0.906,95%CI:0.839-0.979,P=0.013)、白细胞介素18水平(OR=0.924,95%CI:0.866-0.986,P=0.017)和白细胞介素2水平(OR=0.894,95%CI:0.821-0.973,P=0.010)与颈椎间盘退变风险呈直接的负向因果关联。②反向分析结果表明,当颈椎间盘退变作为暴露数据时,与91种炎症蛋白均不具有显著因果关系。③敏感性分析结果显示:双向孟德尔随机化的Cochran’s Q检验、MR-Egger回归法和MR-PRESSO结果P值均大于0.05,表明炎症蛋白与颈椎间盘退变之间的因果效应分析不存在显著的异质性和多效性。④上述结果证实,胶质细胞系源性神经营养因子水平、白细胞介素4水平、单核细胞趋化蛋白1水平、白细胞介素17C水平、白细胞介素18水平和白细胞介素2水平与颈椎间盘退变之间可能具有较为显著的潜在因果关系,这为研究颈椎间盘退变潜在的机制、探索颈椎间盘退变的早期防治以及相关的药物治疗提供了有价值的线索。
BACKGROUND:Cervical disc degeneration is a common degenerative disease,and inflammatory proteins play an important role in cervical disc degeneration,but the specific mechanisms involved remain to be thoroughly investigated.OBJECTIVE:Using the Mendelian randomization method to assess the potential causal relationship between 91 inflammatory proteins and cervical disc degeneration.METHODS:Genome-wide association analysis statistics for 91 inflammatory proteins(from GCST90274758 to GCST90274848)were obtained from the Genome-Wide Association Analysis Catalog of publicly available genome-wide association analysis data and genome-wide association analysis data for cervical disc degeneration from the Finngen database(finngen_R10_M13_CERVICDISCV).Inverse variance weighting,MR-Egger regression,weighted median,weighted modeling,and simple modeling were used to investigate the causal relationship between inflammatory proteins and cervical disc degeneration.Sensitivity analyses were performed to test whether the results of the Mendelian randomization analysis were reliable,and then the inverse Mendelian randomization analysis was performed in the same way.RESULTS AND CONCLUSION:The results of the forward analysis showed that a total of six inflammatory proteins were significantly and causally associated with cervical disc degeneration,of which glial cell lineage-derived neurotrophic factor(odds ratio(OR)=1.095,95%confidence interval(CI):1.012-1.184,P=0.023),interleukin 4(OR=1.094,95%CI:1.002-1.194,P=0.045)and monocyte chemotactic protein-1 levels(OR=1.062,95%CI:1.001-1.127,P=0.048)showed a direct positive causal association with the risk of cervical disc degeneration;interleukin 17C(OR=0.906,95%CI:0.839-0.979,P=0.013),interleukin 18(OR=0.924,95%CI:0.866-0.986,P=0.017)and interleukin 2 levels(OR=0.894,95%CI:0.821-0.973,P=0.010)showed a direct negative causal association with the risk of cervical disc degeneration.The results of the inverse analysis showed that when cervical disc degeneration was used as exposure data,there was no significant causal relationship with any of the 91 inflammatory proteins.The results of the sensitivity analysis showed that the Cochran’s Q test for the two-way Mendelian randomization,the MR-Egger regression method,and the MR-PRESSO results had P values greater than 0.05,indicating that there was no significant heterogeneity or multiplicity in the analysis of the causal effect between inflammatory proteins and cervical disc degeneration.To conclude,there may be a relatively significant potential causal relationship between glial cell line-derived neurotrophic factor,interleukin 4,monocyte chemotactic protein-1,interleukin 17C levels,interleukin 18,and interleukin 2 levels and cervical disc degeneration,which provides valuable clues for research on the potential mechanisms of cervical disc degeneration as well as early prevention and drug treatment of cervical disc degeneration.
作者
刘帅祎
赵晓璇
李奇
邢政
李庆雯
褚晓蕾
Liu Shuaiyi;Zhao Xiaoxuan;Li Qi;Xing Zheng;Li Qingwen;Chu Xiaolei(Tianjin Key Laboratory of Exercise Physiology and Sports Medicine,School of Sport,Exercise&Health,Tianjin University of Sport,Tianjin 300381,China;Department of Rehabilitation,Tianjin Hospital,Tianjin 300000,China)
出处
《中国组织工程研究》
CAS
北大核心
2025年第17期3732-3740,共9页
Chinese Journal of Tissue Engineering Research
基金
国家重点研发计划“生物与信息融合(BT与IT融合)”重点专项项目(2023YFF1205200),项目参与人:邢政
天津市自然科学基金面上项目(22JCYBJC00210),项目负责人:李奇
天津市自然科学基金面上项目(22JCYBJC00220),项目负责人:褚晓蕾。
关键词
颈椎间盘退变
退行性疾病
炎症蛋白
孟德尔随机化
因果关系
遗传学
全基因组关联研究
单核苷酸多态性
cervical disc degeneration
degenerative disease
inflammatory protein
Mendelian randomization
causality
genetics
genome-wide association studies
single nucleotide polymorphism
