血清维生素水平与糖尿病肾病风险：一项孟德尔随机化研究

Serum Vitamin Levels and the Risk of Diabetic Nephropathy: A Mendelian Randomization Study

摘要: 目的：在目前已发表的大量研究中，25羟基维生素D (25OH-D)、维生素B12 (Vit B12)、维生素C (VitC)、维生素E (VitE)水平均与糖尿病肾病严重程度有关，但结论易受混杂偏移及反向因果的影响，本研究的目的是通过孟德尔随机化从基因水平上研究维生素水平与糖尿病肾病的因果关系。方法：从已发表的全基因组关联研究中获得与血清25羟基维生素D (25OH-D)、维生素B12、维生素C和维生素E相关的单核苷酸多态性(snp)，从The FinnGen Biobank中获得与糖尿病肾病相关的汇总水平遗传数据。研究主要使用逆方差加权法(Inverse-Variance Weighted, IVW)进行两样本孟德尔随机化分析。同时采用MR-Egger回归法(MR-Egger regression)、加权中位数法(Weighted Median, WM)、简单模型(Simple Mode)和加权模型(Weighted Mode)法作为MR分析的补充方法，留一法(Leave-one-out sensitivity test)进行敏感性分析。结果：在有关血清维生素水平对糖尿病肾病影响的孟德尔随机化研究(MR)中，IVW方法表明血清25OH-D与糖尿病肾病高风险存在因果关联，尚未发现血清维生素B12、血清维生素C、血清维生素E水平与糖尿病肾病发病风险之间存在因果关联的证据。结论：本研究结果表明血清25OH-D水平与糖尿病肾病高风险之间存在因果联系。

Abstract: Objective: In a large number of published studies, 25 hydroxyvitamin D (25OH-D), vitamin B12 (Vit B12), vitamin C (VitC), and vitamin E (VitE) levels have been associated with the severity of diabetic nephropathy, but the conclusions are susceptible to confounding bias and reverse causation. The aim of this study was to investigate the relationship between vitamin levels and the severity of diabetic nephropathy at the genetic level by Mendelian randomization. Methods: Single nucleotide polymorphisms (snp) associated with serum 25 hydroxyvitamin D (25OH-D), vitamin B12, vitamin C, and vitamin E were obtained from published genome-wide association studies, and pooled-level genetic data associated with diabetic nephropathy were obtained from The FinnGen Biobank. The study focused on two-sample Mendelian randomization analysis using inverse-variance weighted (IVW) method. MR-Egger regression (MR-Egger regression), Weighted median (WM), Simple Mode (Simple Mode) and Weighted Mode (Weighted Mode) methods were also used as complementary methods for MR analysis, and the Leave-one-out sensitivity test was used for sensitivity analysis. Results: In the Mendelian Randomization Study (MR) on the effect of serum vitamin levels on diabetic nephropathy, the IVW methodology demonstrated a causal association between serum 25OH-D and a high risk of diabetic nephropathy, and no evidence has been found for a causal association between serum vitamin B12, serum vitamin C, and serum vitamin E levels and the risk of developing diabetic nephropathy. Conclusion: The results of this study suggest a causal link between serum 25OH-D levels and high risk of diabetic nephropathy.