胰岛素样生长因子家族成员水平对炎性关节炎的影响:基于芬兰生物库分析  

Effect of insulin-like growth factor family member levels on inflammatory arthritis:a FinnGen biobank-based analysis

作　　者：王雪鹏 何勇[1,2] Wang Xuepeng;He Yong(Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai 200052,China)

机构地区：[1]上海中医药大学,上海市201203 [2]上海市光华中西医结合医院,上海市200052

出　　处：《中国组织工程研究》2025年第35期7656-7662,共7页Chinese Journal of Tissue Engineering Research

基　　金：上海市科委“科技创新行动计划”医学创新研究专项(21Y11911400),项目负责人:何勇;上海市长宁区医学硕博士创新人才基地项目(RCJD2022S04),项目负责人:何勇。

摘　　要：背景:研究表明胰岛素样生长因子家族成员与炎性关节炎的发生存在显著关联,但因果关系尚未得到精确表征。目的:探讨胰岛素样生长因子家族成员与强直性脊柱炎、类风湿性关节炎、银屑病关节炎发生发展之间的潜在关联。方法:14个胰岛素样生长因子家族成员相关的遗传工具变量主要源自全基因组关联研究的庞大基因组数据。强直性脊柱炎、类风湿性关节炎和银屑病关节炎的相关汇总统计数据则源自FinnGen联盟的广泛数据集,来自芬兰生物库拥有50万参与者的基因组和健康数据。主要采用逆方差加权法进行孟德尔随机化分析。为了增强研究结果的可信度与广泛适用性,还进行了多种补充分析方法,包括加权中位数法(用于缓解潜在异常值的影响)、MR-Egger回归(用于评估定向多效性)、加权模式与简单模式法(提供因果效应的替代估计)、孟德尔随机化多效性残差和异常值检验(MR-PRESSO)(用于识别并纠正水平多效性)、Cochran’s Q统计量检验(评估效应估计的异质性)以及MR-Egger截距分析(用于检测和调整多效性关系的影响)。结果与结论:鉴定了4个显著的因果关联,包括:CYR61蛋白与强直性脊柱炎(OR:0.919,95%CI:0.848-0.997,P=0.042)和类风湿性关节炎(OR:0.946,95%CI:0.908-0.987,P=0.011)呈负相关;IGF-2R与强直性脊柱炎(OR:0.909,95%CI:0.835-0.990,P=0.029)呈负相关;IGFBP-7与银屑病关节炎(OR:1.104,95%CI:1.002-1.218,P=0.046)呈正相关。敏感性分析结果一致。该研究采用严格的分析方法提供了胰岛素样生长因子家族成员与炎性关节炎风险之间潜在因果关系的证据,有必要进一步研究胰岛素样生长因子家族成员如何影响强直性脊柱炎、类风湿性关节炎和银屑病关节炎的发展机制,为开发针对性干预措施提供依据。此外,通过借鉴国际研究经验,未来中国生物医学研究应进一步聚焦于炎性疾病和免疫相关疾病BACKGROUND:Studies have shown a significant association between members of the insulin-like growth factor family and the occurrence of inflammatory arthritis,but the causal relationship has not been accurately characterized.OBJECTIVE:To explore the potential association between members of the insulin-like growth factor family and the occurrence and development of ankylosing spondylitis,rheumatoid arthritis,and psoriatic arthritis.METHODS:Genetic instrumental variables associated with 14 discrete members of the insulin-like growth factor family,primarily derived from the expansive genomic database of a genome-wide association study,were used.The pertinent summary statistics for ankylosing spondylitis,rheumatoid arthritis,and psoriatic arthritis were meticulously procured from the FinnGen Consortium’s extensive dataset.Our primary analytical methodology was anchored in the inverse-variance weighted approach,which is recognized for its robustness in Mendelian randomization studies.To augment the credibility and broader applicability of the findings,an array of complementary analyses were performed.These encompassed the weighted-median method,which mitigates the influence of potential outliers;the MR-Egger regression,a tool for assessing directional pleiotropy;the weighted mode and simple mode approaches,which provide alternative estimates of the causal effect;the MR pleiotropy residual sum and outlier test,designed to identify and correct for horizontal pleiotropy;Cochran’s Q statistic test,which evaluates the heterogeneity of the effect estimates;and the MR-Egger intercept analysis,a diagnostic for detecting and adjusting the impact of pleiotropic relationships.RESULTS AND CONCLUSION:We identified four distinct causal associations:CYR61 protein was negatively correlated with ankylosing spondylitis(odd ratios[OR]:0.919,95%confidence interval[CI]:0.848-0.997,P=0.042)and rheumatoid arthritis(OR:0.946,95%CI:0.908-0.987,P=0.011);IGF-II receptor was negatively correlated with ankylosing spondylitis(OR:0.909,95%CI:0.8

关 键 词：胰岛素样生长因子 炎症性关节炎 强直性脊柱炎 类风湿性关节炎 银屑病关节炎 孟德尔随机化 因果关系 

分 类 号：R459.9[医药卫生—治疗学] R392.5[医药卫生—临床医学] R684.3