中国组织工程研究

中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (32): 7015-7027.doi: 10.12307/2025.797

• 组织工程相关大数据分析 Big data analysis in tissue engineering • 上一篇    下一篇

不同来源抗氧化剂与骨关节炎：基于欧洲人群全基因组的关联分析

刘小武1，刘金萍2，吴  婷2，贺  宪2，蔡坚雄3   

  1. 1广州中医药大学第二临床医学院，广东省广州市  510120；2广州中医药大学番禺区中医院，广东省广州市  511400；3广州中医药大学第二附属医院，广东省广州市  510120


  • 收稿日期:2024-10-14 接受日期:2024-11-20 出版日期:2025-11-18 发布日期:2025-04-29
  • 通讯作者: 蔡坚雄，主治医师，助理研究员，广州中医药大学第二附属医院，广东省广州市 510120 并列通讯作者：贺宪，主任医师，广州中医药大学番禺区中医院，广东省广州市 511400
  • 作者简介:刘小武，男，1997年生，江西省南昌市人，汉族，广州中医药大学在读博士，主要从事中西医结合临床循证方法学研究。 共同第一作者：刘金萍，女，1997年生，江西省抚州市人，汉族，广州中医药大学在读硕士，主要从事中西医结合骨关节疾病的诊治研究。
  • 基金资助:
    广州市科技计划项目(2024A03J0744)，项目负责人：蔡坚雄；广东省中医院优秀论文支持计划，项目负责人：蔡坚雄

Antioxidants from different sources and osteoarthritis: a genome-wide association analysis in European populations

Liu Xiaowu1, Liu Jinping2, Wu Ting2, He Xian2, Cai Jianxiong3    

  1. 1Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong Province, China; 2Panyu Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 511400, Guangdong Province, China; 3Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong Province, China
  • Received:2024-10-14 Accepted:2024-11-20 Online:2025-11-18 Published:2025-04-29
  • Contact: Cai Jianxiong, Attending physician, Assistant researcher, Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong Province, China Co-corresponding author: He Xian, Chief physician, Panyu Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 511400, Guangdong Province, China
  • About author:Liu Xiaowu, MD candidate, Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong Province, China Liu Jinping, Master candidate, Panyu Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 511400, Guangdong Province, China Liu Xiaowu and Liu Jinping contributed equally to this article.
  • Supported by:
    Guangzhou Science and Technology Planning Project, No. 2024A03J0744 (to CJX); Excellent Paper Support Program of Guangdong Hospital of Traditional Chinese Medicine (to CJX)

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摘要：


文题释义：
抗氧化剂：是一类能够对抗自由基的物质，它们在维持人体健康和抵御多种疾病中扮演着重要角色。人体的氧化反应会产生自由基，这些自由基可以损害细胞和DNA，从而导致老化、炎症或多种疾病。抗氧化剂通过中和自由基，保护细胞免受氧化应激的损伤。
孟德尔随机化：是一种基于遗传变异的研究方法，常用于评估因果关系。在流行病学研究中，孟德尔随机化利用遗传变异作为工具变量来推断暴露因素与结局之间的因果关系。

背景：目前大量观察性研究表明膳食抗氧化剂摄入及体内循环抗氧化剂水平与骨关节炎有关，但这些关联的因果关系尚无充分的阐明。因此，文章拟利用公开的全基因组关联数据，从遗传层面探究膳食抗氧化剂的摄入与体内循环抗氧化剂水平与骨关节炎的因果关联，为骨关节炎的防治提供证据参考。
目的：运用孟德尔随机化方法，评估常见的膳食抗氧化剂(维生素A、C、E和胡萝卜素)与循环抗氧化剂(谷胱甘肽S-转移酶、谷胱甘肽过氧化物酶、过氧化氢酶、超氧化物歧化酶、抗坏血酸、α-生育酚、γ-生育酚、白蛋白、尿酸、胆红素、锌和硒)与骨关节炎潜在的因果关联。
方法：采用公开发表的4种膳食抗氧化剂与12种循环抗氧化剂的全基因组关联分析数据作为暴露因素，以骨关节炎遗传学联盟数据作为结局 (骨关节炎77 052例和健康人群378 169例)。运用逆方差加权法、MR-Egger回归法及加权中位数法评估两者因果效应。采用水平多效性检验与敏感性分析评估结论的稳定性与可信度。
结果与结论：①结果显示膳食维生素C(OR=0.83，95%CI：0.71-0.96，P=0.015)摄入与膝骨关节炎呈负向因果关系，维生素E摄入与膝骨关节炎(OR=1.20，95%CI：1.05-1.34，P=0.004)、膝或髋骨关节炎(OR=1.15，95%CI：1.03-1.27，P=0.008)均呈正向因果关系。②循环抗氧化剂中，白蛋白水平与膝骨关节炎(OR=0.94，95%CI：0.91-0.97，P=0.001)、髋骨关节炎(OR=0.95，95%CI：0.91-0.99，P=0.03)、膝或髋骨关节炎(OR=0.95，95%CI：0.92-0.98，P=0.01)均呈负向因果关系。尿酸与膝骨关节炎(OR=1.10，95%CI：1.03-1.17，P=0.003)呈正向因果关系。③敏感性分析提示结果稳定，且未检测到潜在的水平多效性。④基于欧洲人群全基因组数据发现维生素C摄入可降低膝骨关节炎的风险，血清白蛋白与膝和髋关节炎的风险降低相关，而摄入维生素E和血清尿酸与膝关节炎的风险增加相关。⑤上述结论为骨关节炎的公共健康教育和营养干预提供了证据，并且提示血清白蛋白可能成为骨关节炎风险评估的生物标志物。文章强调了特定抗氧化剂摄入在骨关节炎预防中的重要性，为中国居民的营养指南和公共卫生政策提供了参考依据，为关节炎的生物标志物研究提供了新的线索，有助于开发针对中国人群的早期诊断和风险评估方法。
https://orcid.org/0000-0002-1285-0622(刘小武)；https://orcid.org/020-81887233-35842(蔡坚雄)

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: 抗氧化物, 膝骨关节炎, 髋骨关节炎, 孟德尔随机化, 逆方差加权法, 全基因组关联研究, 因果关系, 单核苷酸多态性

Abstract: BACKGROUND: Currently, numerous observational studies have frequently associated dietary antioxidant intake and circulating antioxidant levels with osteoarthritis. Nevertheless, the underlying causal mechanisms remain unclear. Therefore, this study employs publicly available genome-wide association data to investigate the causal associations between antioxidant intake, circulating levels, and osteoarthritis, offering evidence for the prevention and treatment of osteoarthritis.
OBJECTIVE: To assess the potential causal associations between dietary antioxidants (including vitamins A, C, E, and carotenoids) and circulating antioxidants (such as Glutathione S-transferase, glutathione peroxidase, catalase, superoxide dismutase, ascorbic acid, α-tocopherol, γ-tocopherol, albumin, uric acid, bilirubin, zinc, and selenium) with osteoarthritis through Mendelian randomization. 
METHODS: Data from genome-wide association studies on four dietary antioxidants and twelve circulating antioxidants were employed as exposure variables. The outcome variable was the osteoarthritis consortium dataset, which comprised 77 052 osteoarthritis cases and 378 169 healthy controls. Causal effects were evaluated using the inverse variance-weighted method, MR-Egger regression, and the weighted median approach. Stability and reliability of the findings were assessed through horizontal pleiotropy tests and sensitivity analyses.
RESULTS AND CONCLUSION: (1) These results demonstrated that dietary vitamin C intake was inversely associated with knee osteoarthritis risk (OR=0.83, 95%CI: 0.71-0.96, P=0.015). Conversely, vitamin E intake was positively associated with knee osteoarthritis (OR=1.20, 95%CI: 1.05-1.34, P=0.004) and both knee and hip osteoarthritis (OR=1.15, 95%CI: 1.03-1.27, P=0.008). (2) Circulating antioxidant albumin levels were negatively associated with knee (OR=0.94, 95%CI: 0.91-0.97, P=0.001), hip (OR=0.95, 95%CI: 0.91-0.99, P=0.03), and knee or hip osteoarthritis (OR=0.95, 95%CI: 0.92-0.98, P=0.01). Uric acid levels were positively associated with knee osteoarthritis (OR=1.10, 95%CI: 1.03-1.17, P=0.003). (3) Sensitivity analyses yielded consistent results without evidence of horizontal pleiotropy. (4) European genome-wide data indicated that vitamin C intake was associated with a decreased risk of knee osteoarthritis, and lower serum albumin levels were associated with reduced risks of knee and hip osteoarthritis. In contrast, vitamin E intake and higher serum uric acid were associated with an increased risk of knee osteoarthritis. These findings support public health education and osteoarthritis interventions, indicating that serum albumin could be a potential biomarker for risk assessment. (5) The study underscores the role of certain antioxidants in osteoarthritis prevention and provides evidence to inform nutritional guidelines and public health strategies for the Chinese population. Furthermore, it contributes to biomarker research in arthritis, facilitating the development of early diagnostic tools and risk assessment strategies for the Chinese population.


Key words: antioxidants, knee osteoarthritis, hip osteoarthritis, Mendelian randomization, inverse variance weighting, genome-wide association study, causal association, single nucleotide polymorphism

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