School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
Clin Nutr. 2024 Apr;43(4):1001-1012. doi: 10.1016/j.clnu.2024.03.003. Epub 2024 Mar 7.
BACKGROUND & AIMS: Growing evidence has indicated a potential association between micronutrient levels, urate levels, and the risk of gout. However, the causal association underlying these associations still remains uncertain. Previous observational studies and randomized controlled trials investigating the association between micronutrients, urate levels, and the risk of gout have been limited in their scope and depth. The aim of this study was to utilize Mendelian randomization (MR) to investigate the causal associations between genetically predicted micronutrient levels, urate levels, and the risk of gout. METHODS: In this study, we conducted a comprehensive examination of 10 specific micronutrients (vitamin B, vitamin B, vitamin C, vitamin D, folate, calcium, iron, copper, zinc, and selenium) as potential exposures. Two-sample MR analyses were performed to explore their causal associations with urate levels and the risk of gout. In these analyses, gout data were collected from the Global Biobank Meta-Analysis Initiative (N = 1,069,839, N cases = 30,549) and urate levels data from CKDGen Consortium (N = 288,649) by utilizing publicly available summary statistics from independent cohorts of European ancestry. We performed inverse-variance weighted MR analyses as main analyses, along with a range of sensitivity analyses, such as MR-Egger, weighted median, simple mode, weighted mode, Steiger filtering, MR-PRESSO, and Radial MR analysis, to ensure the robustness of our findings. RESULTS: The results of our study indicate that there were negative associations between serum vitamin B and urate levels, as well as serum folate and the risk of gout. Specifically, we found a negative association between vitamin B levels and urate levels, with a β coefficient of -0.324 (95% CI -0.0581 to -0.0066, P = 0.0137) per one standard deviation (SD) increase. Similarly, a negative association was observed between folate levels and gout risk, with an odds ratio of 0.8044 (95% CI 0.6637 to 0.9750, P = 0.0265) per one SD increase. On the other hand, we identified positive associations between serum calcium levels and both urate levels and the risk of gout. Specifically, there was a positive association between serum calcium levels and urate levels (β coefficient: 0.0994, 95% CI 0.0519 to 0.1468, P = 4.11E-05) per one SD increase. Furthermore, a positive association was found between serum calcium levels and the risk of gout, with an odds ratio of 1.1479 (95% CI 1.0460 to 1.2598, P = 0.0036) per one SD increase. These findings were robust in extensive sensitivity analyses. By employing MR-PRESSO and Radial MR to eliminate outliers, the observed associations have been reinforced. No clear associations were found between the other micronutrients and the urate levels, as well as the risk of gout. CONCLUSION: Our findings provided evidence that there were negative associations between serum vitamin B and urate levels, as well as serum folate and the risk of gout, while positive associations existed between the serum calcium levels and urate levels, as well as the risk of gout.
背景与目的:越来越多的证据表明,微量营养素水平、尿酸水平与痛风风险之间存在潜在关联。然而,这些关联背后的因果关系仍不确定。之前观察性研究和随机对照试验对微量营养素、尿酸水平与痛风风险之间的关联进行了研究,但范围和深度有限。本研究旨在利用孟德尔随机化(MR)来研究遗传预测的微量营养素水平、尿酸水平与痛风风险之间的因果关系。
方法:本研究全面考察了 10 种特定的微量营养素(维生素 B1、维生素 B2、维生素 C、维生素 D、叶酸、钙、铁、铜、锌和硒)作为潜在暴露因素。进行两样本 MR 分析以探讨它们与尿酸水平和痛风风险的因果关系。在这些分析中,痛风数据来自全球生物银行荟萃分析倡议(N=1069839,N 病例=30549),尿酸水平数据来自 CKDGen 联盟(N=288649),利用来自欧洲血统独立队列的公开可用汇总统计数据。我们进行了逆方差加权 MR 分析作为主要分析,并进行了一系列敏感性分析,如 MR-Egger、加权中位数、简单模式、加权模式、Steiger 过滤、MR-PRESSO 和径向 MR 分析,以确保研究结果的稳健性。
结果:我们的研究结果表明,血清维生素 B 与尿酸水平以及血清叶酸与痛风风险之间存在负相关。具体来说,我们发现维生素 B 水平与尿酸水平之间存在负相关,每增加一个标准差(SD),β系数为-0.324(95%CI-0.0581 至-0.0066,P=0.0137)。同样,叶酸水平与痛风风险之间也存在负相关,优势比为 0.8044(95%CI0.6637 至 0.9750,P=0.0265)。另一方面,我们发现血清钙水平与尿酸水平和痛风风险之间存在正相关。具体来说,血清钙水平与尿酸水平之间存在正相关(β系数:0.0994,95%CI0.0519 至 0.1468,P=4.11E-05),每增加一个 SD。此外,血清钙水平与痛风风险之间也存在正相关,优势比为 1.1479(95%CI1.0460 至 1.2598,P=0.0036)。这些发现经过广泛的敏感性分析后仍然稳健。通过使用 MR-PRESSO 和径向 MR 消除异常值,观察到的关联得到了加强。其他微量营养素与尿酸水平以及痛风风险之间没有明显关联。
结论:我们的研究结果表明,血清维生素 B 与尿酸水平之间以及血清叶酸与痛风风险之间存在负相关,而血清钙水平与尿酸水平以及痛风风险之间存在正相关。
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