Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Institute of Urology, Anhui Medical University, Hefei, Auhui, China.
BMC Urol. 2024 Aug 28;24(1):182. doi: 10.1186/s12894-024-01568-8.
Urolithiasis is a highly prevalent global disease closely associated with metabolic factors; however, the causal relationship between blood metabolites and urolithiasis remains poorly understood.
In our study, we employed a bi-directional two-sample Mendelian randomization (MR) analysis to investigate the causal associations between urolithiasis and metabolites. The random-effects inverse-variance weighted (IVW) estimation method was utilized as the primary approach, complemented by several other estimators including MR-Egger, weighted median, colocalization and MR-PRESSO. Furthermore, the study included replication and meta-analysis. Finally, we conducted metabolic pathway analysis to elucidate potential metabolic pathways.
After conducting multiple tests for correction, glycerol might contribute to the urolithiasis and dehydroisoandrosterone sulfate (DHEA-S) might inhibit this process. Furthermore, several blood metabolites had shown potential associations with a causal relationship. Among the protective metabolites were lipids (dehydroisoandrosterone sulfate and 1-stearoylglycerol (1-monostearin)), amino acids (isobutyrylcarnitine and 2-aminobutyrate), a keto acid (acetoacetate) and a carbohydrate (mannose). The risk metabolites included lipids (1-palmitoylglycerophosphoethanolamine, glycerol and cortisone), a carbohydrate (erythronate), a peptide (pro-hydroxy-pro) and a fatty acid (eicosenoate). In reverse MR analysis, urolithiasis demonstrated a statistically significant causal relationship with butyrylcarnitine, 3-methyl-2-oxobutyrate, scyllo-inositol, leucylleucine and leucylalanine. However, it was worth noting that none of the blood metabolites exhibited statistical significance after multiple corrections. Additionally, we identified one metabolic pathway associated with urolithiasis.
The results we obtained demonstrate the causal relevance between two metabolites and urolithiasis, as well as identify one metabolic pathway potentially associated with its development. Given the high prevalence of urolithiasis, further investigations are encouraged to elucidate the mechanisms of these metabolites and explore novel therapeutic strategies.
尿石症是一种在全球范围内普遍存在的疾病，与代谢因素密切相关；然而，血液代谢物与尿石症之间的因果关系仍知之甚少。
在我们的研究中，我们采用双向双向孟德尔随机化（MR）分析来研究尿石症与代谢物之间的因果关系。采用随机效应逆方差加权（IVW）估计方法作为主要方法，并用其他几种估计器（包括 MR-Egger、加权中位数、共定位和 MR-PRESSO）进行补充。此外，还进行了复制和荟萃分析。最后，我们进行了代谢途径分析以阐明潜在的代谢途径。
经过多次校正测试，甘油可能导致尿石症，而去氢表雄酮硫酸盐（DHEA-S）可能抑制这一过程。此外，一些血液代谢物显示出与因果关系相关的潜在关联。具有保护作用的代谢物包括脂质（去氢表雄酮硫酸盐和 1-硬脂酰甘油（1-硬脂酸单甘酯））、氨基酸（异丁酰肉碱和 2-氨基丁酸）、酮酸（乙酰乙酸盐）和碳水化合物（甘露糖）。风险代谢物包括脂质（1-棕榈酰甘油磷酸乙醇胺、甘油和皮质酮）、碳水化合物（赤藓糖）、肽（脯氨酸-羟基-脯氨酸）和脂肪酸（二十碳烯酸）。在反向 MR 分析中，尿石症与丁酰肉碱、3-甲基-2-氧代丁酸、鲨肌醇、亮氨酰亮氨酸和亮氨酰丙氨酸呈显著的因果关系。然而，值得注意的是，经过多次校正后，没有一种血液代谢物具有统计学意义。此外，我们确定了一个与尿石症相关的代谢途径。
我们的研究结果表明，两种代谢物与尿石症之间存在因果关系，并确定了一个可能与尿石症发展相关的代谢途径。鉴于尿石症的高患病率，鼓励进一步研究这些代谢物的机制，并探索新的治疗策略。
