中国组织工程研究

中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (24): 5263-5271.doi: 10.12307/2025.758

• 组织构建相关数据分析 Date analysis of organization construction • 上一篇    下一篇

类风湿关节炎与冠状动脉粥样硬化：欧洲人群血清代谢物和炎症因子数据分析

张艺博1，卢健棋2，毛美玲1，庞  延1，董  礼1，杨尚冰1，肖  湘1   

  1. 1广西中医药大学，广西壮族自治区南宁市  530000；2广西中医药大学第一附属医院心内科，国家中医心血管病临床医学研究中心分中心，广西壮族自治区南宁市  530000
  • 收稿日期:2024-10-10 接受日期:2024-11-16 出版日期:2025-08-28 发布日期:2025-02-06
  • 通讯作者: 卢健棋，教授，博士生导师，广西中医药大学第一附属医院心内科，国家中医心血管病临床医学研究中心分中心，广西壮族自治区南宁市 530000
  • 作者简介:张艺博，女，1997年生，黑龙江省哈尔滨市人，汉族，广西中医药大学在读硕士，主要从事心血管疾病防治研究。
  • 基金资助:
    国家自然科学基金地区基金(82160887)，项目负责人：卢健棋；国家中医临床研究基地业务建设第二批科研专项课题(JDZX2015146)，项目负责人：卢健棋；国家中医药传承创新中心项目(2023019-10)，项目负责人：卢健棋；广西自然科学基金(2021GXNSFAA220111)，
    项目负责人：卢健棋；广西岐黄学者培养项目(2024005-06-02)，项目负责人：卢健棋；广西中医药管理局自筹经费科研课题(GXZYA20230065)，项目负责人：卢健棋；广西高水平中医药重点学科-中医心病学(2024016-02-02)，项目负责人：卢健棋

Rheumatoid arthritis and coronary atherosclerosis: data analysis of serum metabolite and inflammatory factor in the European population

Zhang Yibo1, Lu Jianqi2, Mao Meiling1, Pang Yan1, Dong Li1, Yang Shangbing1, Xiao Xiang1   

  1. 1Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China; 2Department of Cardiology, the First Affiliated Hospital of Guangxi University of Chinese Medicine, National Clinical Research Center for Chinese Medicine Cardiology, Nanning 530000, Guangxi Zhuang Autonomous Region, China
  • Received:2024-10-10 Accepted:2024-11-16 Online:2025-08-28 Published:2025-02-06
  • Contact: Lu Jianqi, Professor, Doctoral supervisor, Department of Cardiology, the First Affiliated Hospital of Guangxi University of Chinese Medicine, National Clinical Research Center for Chinese Medicine Cardiology, Nanning 530000, Guangxi Zhuang Autonomous Region, China
  • About author:Zhang Yibo, Master’s candidate, Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China
  • Supported by:
    National Natural Science Foundation of China Regional Fund, No. 82160887 (to LJQ); The Second Batch of Scientific Research Projects for the Business Construction of the National Clinical Research Base of Traditional Chinese Medicine, No. JDZX2015146 (to LJQ); National Traditional Chinese Medicine Inheritance and Innovation Center Project, No. 2023019-10 (to LJQ); Natural Science Foundation of Guangxi Zhuang Autonomous Region, No. 2021GXNSFAA220111 (to LJQ); Guangxi Qihuang Scholar Training Project, No. 2024005-06-02 (to LJQ); Guangxi Administration of Traditional Chinese Medicine Self-funded Research Project, No. GXZYA20230065 (to LJQ); Key Discipline of High-Level Traditional Chinese Medicine in Guangxi Zhuang Autonomous Region - Traditional Chinese Medicine Cardiology, No. 2024016-02-02 (to LJQ)

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摘要：


文题释义：
孟德尔随机化：是一种利用遗传变异作为工具变量来探索暴露与结果的因果关系的方法，具有低成本、少时间、可行性高的优点，并且不易受到社会和心理因素等混杂因素的影响，可以最大程度地避免观察性研究中的反向因果偏差。
类风湿关节炎：是一种持久的免疫系统疾病，特征是关节炎症和不适。炎症与类风湿关节炎和冠状动脉粥样硬化均相关，表明这些疾病之间可能存在共同的病理生理途径。

背景：类风湿关节炎与冠状动脉粥样硬化之间的关系受到广泛关注，炎症与类风湿关节炎和冠状动脉粥样硬化均相关，表明这两种疾病之间可能存在共同的病理生理途径，但观察性研究尚未阐明因果关系。
目的：通过孟德尔随机化分析探讨类风湿关节炎与冠状动脉粥样硬化之间是否存在因果关系，以及与1 400种血清代谢物和91种炎症因子之间的潜在因果关联。
方法：冠状动脉粥样硬化数据来自Finngen数据库，类风湿关节炎数据来自IEU OpenGWAS数据库，血清代谢物数据来自加拿大老龄化纵向研究、奥格斯堡地区合作健康研究和英国双胞胎项目研究，91种炎症蛋白数据来源于2023年发表在《Nature Immunology》的研究。使用全基因组关联研究的数据进行孟德尔随机化分析，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评估因果效应，其中逆方差加权法是主要分析方法。为了增强稳健性，使用Cochran’s Q检验MR-Egger截距进行敏感性分析。
结果与结论：①逆方差加权分析结果显示，类风湿关节炎与冠状动脉粥样硬化相对风险增加呈正相关(OR=1.002，95%CI=1.001-1.003，P=0.003)；冠状动脉粥样硬化与类风湿关节炎不存在反向因果关系；96种血清代谢物和9种炎症因子与冠状动脉粥样硬化之间存在因果关系；51种血清代谢物和7种炎症因子与类风湿关节炎之间存在因果关系。②研究提供了类风湿关节炎与冠状动脉粥样硬化之间的流行病学证据，强调了血清代谢物和炎症因子在这些疾病的发病机制中的潜在作用，可能有助于开发新的治疗策略。由于对亚洲人群数据收录有限，当下研究多采用国际数据库、欧洲群体分析，通过收集和分析欧洲人群的健康数据，有利于更好地理解中国医学在欧洲的应用效果和潜在影响，进一步推进现代中西医结合的实践；同时通过与欧洲数据库的比较研究，可以揭示不同人群间的遗传差异和疾病易感性，为全球健康研究提供更多维度和视角。
https://orcid.org/0009-0009-0595-8852(张艺博)

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

关键词: 类风湿关节炎, 冠状动脉粥样硬化, 血清代谢物, 炎症因子, 因果关系, 孟德尔随机化分析, 工程化组织构建

Abstract: BACKGROUND: The relationship between rheumatoid arthritis and coronary atherosclerosis has received extensive attention. Inflammation is related to rheumatoid arthritis and coronary atherosclerosis, indicating that there may be a common pathophysiological pathway between the two diseases. However, observational studies have not yet clarified the causal relationship.
OBJECTIVE: To explore whether there is a causal relationship between rheumatoid arthritis and coronary atherosclerosis, as well as the potential causal relationship with 1 400 serum metabolites and 91 inflammatory factors through a Mendelian randomization analysis.
METHODS: Coronary atherosclerosis data are from Finngen database, rheumatoid arthritis data are from IEU OpenGWAS database, serum metabolites data are from Canadian Longitudinal Study on Aging, Augsburg Cooperative Health Research and British Twin Project Research, and data of 91 inflammatory proteins are from research published in Nature Immunology in 2023. Mendelian randomization analysis was performed using data from genome-wide association studies, and causal effects were evaluated using inverse variance weighting, MR-Egger regression, weighted median, weighted model, and simple model methods, with inverse variance weighting being the primary analysis method. To enhance robustness, Cochran’s Q-test MR-Egger intercept was used for sensitivity analysis.
RESULTS AND CONCLUSION: (1) Inverse variance weighting results showed that rheumatoid arthritis was positively correlated with the increased relative risk of coronary atherosclerosis (odds ratio=1.002, 95% confidence interval=1.001-1.003, P=0.003). There was no reverse causal relationship between coronary atherosclerosis and rheumatoid arthritis. In addition, 96 serum metabolites and 9 inflammatory factors were found to have causal relationships with coronary atherosclerosis. There was a causal relationship between 51 serum metabolites and 7 inflammatory factors and rheumatoid arthritis. (2) This study provided epidemiological evidence between rheumatoid arthritis and coronary atherosclerosis, and emphasized the potential role of serum metabolites and inflammatory factors in the pathogenesis of these diseases. These findings may contribute to the development of new treatment strategies. Due to the limited inclusion of data from Asian populations, most contemporary studies used international databases and European population analyses. By collecting and analyzing the health data of European populations, it is conducive to a better understanding of the effects and potential role of Chinese medicine in Europe, and to further promote the practice of modern integration of Western and Chinese medicine. Meanwhile, through the comparative study with the European databases, it is possible to reveal the genetic differences and susceptibility to diseases among different populations, providing more dimensions and perspectives for global health research.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: rheumatoid arthritis, coronary atherosclerosis, serum metabolites, inflammatory factors, causality, Mendelian randomization analysis, engineered tissue construction

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