Tang Yidan, Xu Xiaolin, Zhang Shuangyi, Kong Weishuang, Zhang Weiyi, Zhu Tao
Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.
Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.
Front Nutr. 2023 Dec 21;10:1233086. doi: 10.3389/fnut.2023.1233086. eCollection 2023.
Although well-documented, the causal relationships between diet-derived circulating antioxidants, oxidative stress, and osteoarthritis (OA) are equivocal. The objective of this study is to employ two-sample Mendelian randomization (MR) to investigate possible causal relationships among dietary-derived circulating antioxidants, oxidative stress damage indicators, and OA risk.
Single-nucleotide polymorphisms for diet-derived circulating antioxidants (ascorbate, β-carotene, lycopene, retinol, and α-and γ-tocopherol), assessed as absolute levels and metabolites, as well as oxidative stress injury biomarkers (GSH, GPX, CAT, SOD, albumin, and total bilirubin), were retrieved from the published data and were used as genetic instrumental variables. Summary statistics for gene-OA associations were obtained from publicly available and two relatively large-scale GWAS meta-analyses to date. The inverse-variance weighting method was utilized as the primary MR analysis. Moreover, multivariable MR was used to determine if mediators (BMI and smoking) causally mediated any connection. Furthermore, for each exposure, MR analyses were conducted per outcome database and then meta-analyzed.
Genetically predicted absolute retinol level was causally associated with hip OA risk [odds ratios (ORs) = 0.40, 95% confidence interval (CI) = 0.24-0.68, FDR-corrected = 0.042]. Moreover, genetically predicted albumin level was causally associated with total OA risk (OR = 0.80, 95% CI = 0.75-0.86, FDR-corrected = 2.20E-11), as well as the risk of hip OA (OR = 0.75, 95% CI = 0.68-0.84, FDR-corrected = 1.38E-06) and knee OA (OR = 0.82, 95% CI = 0.76-0.89, FDR-corrected = 4.49E-06). In addition, MVMR confirmed that the effect of albumin on hip OA is independent of smoking initiation, alcoholic drinks per week, and moderate-to-vigorous physical activity levels but may be influenced by BMI.
Evidence from our study supports a potentially protective effect of high levels of retinol and albumin on OA risk.
尽管有充分的文献记载，但饮食来源的循环抗氧化剂、氧化应激与骨关节炎（OA）之间的因果关系并不明确。本研究的目的是采用两样本孟德尔随机化（MR）方法，研究饮食来源的循环抗氧化剂、氧化应激损伤指标与OA风险之间可能存在的因果关系。
从已发表的数据中检索饮食来源的循环抗氧化剂（抗坏血酸、β-胡萝卜素、番茄红素、视黄醇以及α-和γ-生育酚）的单核苷酸多态性，这些抗氧化剂以绝对水平和代谢产物形式进行评估，同时检索氧化应激损伤生物标志物（谷胱甘肽、谷胱甘肽过氧化物酶、过氧化氢酶、超氧化物歧化酶、白蛋白和总胆红素）的单核苷酸多态性，并将其用作遗传工具变量。基因与OA关联的汇总统计数据来自公开可用的以及迄今为止两个相对大规模的全基因组关联研究（GWAS）荟萃分析。采用逆方差加权法作为主要的MR分析方法。此外，使用多变量MR来确定中介因素（体重指数和吸烟）是否因果介导了任何关联。此外，对于每种暴露因素，针对每个结局数据库进行MR分析，然后进行荟萃分析。
基因预测的视黄醇绝对水平与髋部OA风险存在因果关联[比值比（OR）=0.40，95%置信区间（CI）=0.24 - 0.68，经FDR校正 = 0.042]。此外，基因预测的白蛋白水平与总OA风险存在因果关联（OR = 0.80，95% CI = 0.75 - 0.86，经FDR校正 = 2.20E - 11），以及与髋部OA风险（OR = 0.75，95% CI = 0.68 - 0.84，经FDR校正 = 1.38E - 06）和膝部OA风险（OR = 0.82，95% CI = 0.76 - 0.89，经FDR校正 = 4.49E - 06）存在因果关联。此外，多变量MR证实白蛋白对髋部OA的影响独立于开始吸烟、每周饮酒量以及中度至剧烈身体活动水平，但可能受体重指数影响。
我们研究的证据支持高水平视黄醇和白蛋白对OA风险具有潜在保护作用。
