AUTHOR=Zhu Wuhui , Li Huan , Zhang Ming , Ji Bing , Liu Zongtao TITLE=Plasma metabolites as potential markers and targets to prevent and treat urolithiasis: a Mendelian randomization study JOURNAL=Frontiers in Molecular Biosciences VOLUME=11 YEAR=2024 URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2024.1426575 DOI=10.3389/fmolb.2024.1426575 ISSN=2296-889X ABSTRACT=Background

Studies 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.

Objective

The objective of the study was to investigate the potential risks of plasma metabolites in urolithiasis using a two-sample Mendelian randomization (MR) study.

Methods

A 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.

Results

For 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).

Conclusions

Our 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.