Department of Endocrinology, The First People's Hospital of Kunshan, Kunshan, Jiangsu 215300, China.
Department of Clinical Nutrition, The First People's Hospital of Kunshan, Kunshan, Jiangsu 215300, China.
J Diabetes Res. 2024 Oct 30;2024:6828908. doi: 10.1155/2024/6828908. eCollection 2024.
Our goal was to examine the causal link between blood metabolites, their ratios, and the risk of developing proliferative diabetic retinopathy (PDR) from a genetic insight. Summary-level data about 1400 blood metabolites and their ratios, as well as PDR, were sourced from prior genome-wide association studies (GWAS). A two-sample univariate and multivariate Mendelian randomization (MR) approach was utilized. Additionally, metabolic pathway analysis and sensitivity analysis were also conducted. After adjusting for multiple tests, four blood metabolites significantly correlated with PDR risk. Two ceramides, including glycosyl-N-palmitoyl-sphingosine (d18:1/16:0) (odds ratio [OR] = 1.12, 95% confidence interval (CI): 1.06-1.17, < 0.001, false discovery rate (FDR) = 0.005) and glycosyl-N-behenoyl-sphingadienine (d18:2/22:0) (OR = 1.11, 95% CI: 1.06-1.16, < 0.001, FDR = 0.017), were linked to increased risk. Additionally, 3-methylcytidine (OR = 1.05, 95% CI: 1.03-1.08, < 0.001, FDR = 0.021) also posed a risk, whereas (N(1)+N(8))-acetylspermidine (OR = 0.91, 95% CI: 0.87-0.94, < 0.001, FDR = 0.002) appeared protective. Multivariable MR analysis further confirmed a direct, protective effect of (N(1)+N(8))-acetylspermidine on PDR risk (OR = 0.94, 95% CI: 0.89-1.00, = 0.040). The sensitivity analysis results indicated that evidence for heterogeneity and pleiotropy was absent. These metabolites have the potential to be used as biomarkers and are promising for future research into the mechanisms and drug targets for PDR.
我们的目标是从遗传角度研究血液代谢物及其比值与增殖性糖尿病视网膜病变（PDR）发病风险之间的因果关系。先前的全基因组关联研究（GWAS）提供了关于 1400 种血液代谢物及其比值和 PDR 的汇总水平数据。采用两样本单变量和多变量孟德尔随机化（MR）方法。此外，还进行了代谢途径分析和敏感性分析。在进行多次检验调整后，有 4 种血液代谢物与 PDR 风险显著相关。两种神经酰胺，包括神经酰胺 N-棕榈酰基-β-D-葡萄糖基-1-鞘氨醇（d18:1/16:0）（比值比[OR] = 1.12，95%置信区间[CI]：1.06-1.17，<0.001，假发现率[FDR] = 0.005）和神经酰胺 N-二十二碳烯酰基-β-D-高半胱氨酰鞘氨醇（d18:2/22:0）（OR = 1.11，95% CI：1.06-1.16，<0.001，FDR = 0.017）与风险增加相关。此外，3-甲基胞嘧啶（OR = 1.05，95% CI：1.03-1.08，<0.001，FDR = 0.021）也存在风险，而 N（1）+N（8））-乙酰基腐胺（OR = 0.91，95% CI：0.87-0.94，<0.001，FDR = 0.002）呈保护作用。多变量 MR 分析进一步证实了 N（1）+N（8））-乙酰基腐胺对 PDR 风险的直接保护作用（OR = 0.94，95% CI：0.89-1.00，P=0.040）。敏感性分析结果表明，不存在异质性和多效性的证据。这些代谢物有可能作为生物标志物，并有望为未来研究 PDR 的发病机制和药物靶点提供依据。
