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  

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

作　　者：刘小武 刘金萍 吴婷 贺宪 蔡坚雄 Liu Xiaowu;Liu Jinping;Wu Ting;He Xian;Cai Jianxiong(Second Clinical Medical College,Guangzhou University of Chinese Medicine,Guangzhou 510120,Guangdong Province,China;Panyu Hospital of Traditional Chinese Medicine,Guangzhou University of Chinese Medicine,Guangzhou 511400,Guangdong Province,China;Second Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510120,Guangdong Province,China)

机构地区：[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

出　　处：《中国组织工程研究》2025年第32期7015-7027,共13页Chinese Journal of Tissue Engineering Research

基　　金：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~~。

摘　　要：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77052例和健康人群378169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 77052 osteoarthritis cases and 378169 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)

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 

分 类 号：R452[医药卫生—治疗学] R318[医药卫生—临床医学] R684.3