Fu Canya, Liu Bin, Chen Weiwei, Qiu Yu, Zheng Canjie, Mao Yingying, Yin Zhiying, Ye Ding
School of Public Health, Zhejiang Chinese Medical University, Hangzhou, China.
Department of Immunity, Quzhou Center for Disease Control and Prevention, Quzhou, China.
Food Funct. 2025 Jan 20;16(2):707-719. doi: 10.1039/d4fo00294f.
. Previous observational studies have provided inconsistent evidence for the association between serum iron status and the risk of gout. Moreover, it remains uncertain whether the observed association is causal or due to confounding or reverse causality. This research aimed to investigate the association of serum iron status indicators with the risk of gout and to further examine the causal relationship by the Mendelian randomization (MR) method. We first conducted a cross-sectional study from the National Health and Nutrition Examination Survey 2017-2018, including a total of 4635 participants. The association of serum iron status indicators with gout risk was evaluated using a multivariable logistic regression model. Furthermore, a two-sample MR study using genetic data from large-scale genome-wide association studies of serum iron status indicators (246 139 individuals) and gout (discovery: 13 179 cases and 75 0634 controls; replication: 5292 cases and 368 788 controls; 2115 cases and 67 259 controls) was conducted to infer causality. Inverse-variance-weighting (IVW) was applied as the main method of MR analysis. A series of sensitivity analyses were used to evaluate the robustness of their relationship. In the cross-sectional study, there was no significant relationship between serum iron status indicators and gout risk. However, IVW results showed that genetically predicted serum iron and transferrin saturation (TSAT) were significantly associated with the increased risk of gout in the discovery analysis [odds ratio (OR): 1.21; 95% confidence interval (CI): 1.10-1.32; = 9.80 × 10 for serum iron and OR: 1.16; 95% CI: 1.08-1.25; = 7.14 × 10 for TSAT]. The replication analysis provided similar results compared with the discovery analysis. Our study provides support for potential causal associations between serum iron and the altered risk of gout. Further investigations are warranted to elucidate the biological processes through which iron influences susceptibility to gout.
以往的观察性研究对于血清铁状态与痛风风险之间的关联提供了不一致的证据。此外，观察到的这种关联是因果关系、还是由于混杂因素或反向因果关系导致的，仍不确定。本研究旨在调查血清铁状态指标与痛风风险之间的关联，并通过孟德尔随机化（MR）方法进一步检验因果关系。我们首先对2017 - 2018年美国国家健康与营养检查调查进行了一项横断面研究，共纳入4635名参与者。使用多变量逻辑回归模型评估血清铁状态指标与痛风风险之间的关联。此外，利用来自血清铁状态指标（246139人）和痛风的大规模全基因组关联研究的基因数据进行了一项两样本MR研究（发现阶段：13179例病例和750634例对照；重复阶段：5292例病例和368788例对照；2115例病例和67259例对照）以推断因果关系。采用逆方差加权（IVW）作为MR分析的主要方法。使用一系列敏感性分析来评估它们关系的稳健性。在横断面研究中，血清铁状态指标与痛风风险之间没有显著关系。然而，IVW结果显示，在发现分析中，基因预测的血清铁和转铁蛋白饱和度（TSAT）与痛风风险增加显著相关[比值比（OR）：1.21；95%置信区间（CI）：1.10 - 1.32；血清铁的P = 9.80×10 ，TSAT的OR：1.16；95%CI：1.08 - 1.25；P = 7.14×10 ]。重复分析与发现分析提供了相似的结果。我们的研究为血清铁与痛风风险改变之间的潜在因果关联提供了支持。有必要进一步研究以阐明铁影响痛风易感性的生物学过程。
