Plasma metabolites as potential markers and targets to prevent and treat urolithiasis: a Mendelian randomization study

IF 3.9 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Frontiers in Molecular Biosciences Pub Date : 2024-08-27 DOI:10.3389/fmolb.2024.1426575

Wuhui Zhu, Huan Li, Ming Zhang, Bing Ji, Zongtao Liu

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Abstract

BackgroundStudies on the relationships between diseases of the urinary system and human plasma proteomes have identified several potential biomarkers. However, none of these studies have elucidated the causal relationships between plasma proteins and urolithiasis.ObjectiveThe objective of the study was to investigate the potential risks of plasma metabolites in urolithiasis using a two-sample Mendelian randomization (MR) study.MethodsA total of 1,400 metabolites were identified in the most comprehensive genome-wide association study (GWAS) of plasma metabolomics in a European population to date, and single-nucleotide polymorphisms (SNPs) were used as the instrumental variables for the plasma metabolites. The European GWAS data for urinary calculi included 482,123 case samples and 6,223 control samples (ebi-a-GCST90018935). The associations between the plasma metabolites and risk of urolithiasis were evaluated by inverse variance weighting (IVW) and supplemented by sensitivity analyses of the MR-Egger and MR-PRESSO tests.ResultsFor the first time, we found a causal relationship between two plasma metabolites (p < 1.03 × 10−4) and urolithiasis (p < 0.05). The chemical 4-hydroxychlorothalonil, which is an intermediate product of the pesticide hydroxychlorothalonil, could promote urolithiasis (odds ratio (OR) = 1.12) as a risk factor. Moreover, 1-stearoyl-2-arachidonoyl-GPC, which is an important component of phospholipid metabolism in the human body, can inhibit urolithiasis (OR = 0.94).ConclusionsOur results suggest that blood metabolites can be used as blood markers and drug targets in the prevention, diagnosis, and treatment of urolithiasis; furthermore, our results can provide a basis for policy makers to formulate prevention and treatment policies for urolithiasis.

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血浆代谢物作为预防和治疗尿路结石的潜在标志物和靶点：孟德尔随机研究

背景有关泌尿系统疾病与人体血浆蛋白质组之间关系的研究发现了几种潜在的生物标志物。本研究的目的是通过双样本孟德尔随机化（MR）研究，探讨血浆代谢物在泌尿系统疾病中的潜在风险。方法在迄今为止最全面的欧洲人群血浆代谢组学全基因组关联研究（GWAS）中共鉴定了1400种代谢物，并将单核苷酸多态性（SNPs）作为血浆代谢物的工具变量。欧洲泌尿系结石 GWAS 数据包括 482 123 个病例样本和 6223 个对照样本（ebi-a-GCST90018935）。结果我们首次发现两种血浆代谢物（p&p;lt; 1.03 × 10-4）与尿路结石（p&p;lt; 0.05）之间存在因果关系。化学物质 4-hydroxychlorothalonil 是农药 hydroxychlorothalonil 的中间产物，可作为风险因素促进尿崩症的发生（几率比（OR）= 1.12）。结论：我们的研究结果表明，血液代谢物可作为预防、诊断和治疗尿石症的血液标记物和药物靶标；此外，我们的研究结果还可为决策者制定尿石症预防和治疗政策提供依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Molecular Biosciences Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

7.20

自引率

4.00%

发文量

1361

审稿时长

14 weeks

期刊介绍： Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology. Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life. In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.