Work

Exploration of the association of antidiabetic drugs with urolithiasis: A drug-targeted Mendelian randomization study

Year: 2025

Type: article

Abstract: Objective Type 2 diabetes mellitus (T2DM) have previously been reported to be potentially associated with urolithiasis. We conducted a Mendelian randomization (MR) study to explore whether there is a causal relationship between genetic susceptibility to common antidiabetic drugs and urolithiasis risks. Methods We use genetic variants from two different sources as anti-diabetic drugs for our MR research design. The variants include loci regulating expression traits of these target genes, and genetic variants for blood glucose nearby or within antidiabetic drug target genes from the genome-wide association study. We ultimately calculated estimates using inverse variance weighted MR (IVW-MR) and summary data-based MR methods. Results The Bonferroni-corrected IVW results suggested potassium inwardly rectifying channel, subfamily J, member 11 ( KCNJ11 )-mediated blood glucose was associated with a lower risk of urolithiasis (odds ratio [OR]: 0.15; 95% confidence interval [CI]: 0.06, 0.39; p <0.001). Similarly, we also observed a higher expression of KCNJ11 was linked to a decreased risk of urolithiasis in the summary data-based MR analysis (OR: 0.81 per 1 mmol/L decrement in blood glucose; 95% CI: 0.70, 0.95; p =0.008). We found a suggestive evidence of the positive relationship between insulin receptor expression and urolithiasis (OR: 5.67; 95% CI: 1.01, 31.97; p =0.049), but which was not supported when using cis -expression quantitative trait locus as an instrument. Conclusion This study provided evidence for a potential causal link between KCNJ11 -mimicked sulfonylureas and the reduced risk of urolithiasis. Given the limitations of this study, it is essential to investigate further using the latest data from large-scale genetic studies and relevant clinical data to validate our findings from the MR study.

Source: Asian journal of urology

DOI: 10.1016/j.ajur.2025.03.012

Authors: Xidong Wang, Qiancheng Mao, Tianqi Wang, Yingying Yang, Ming Liu, Jitao Wu

Institutions: Qingdao University, Yuhuangding Hospital

Language: English

Topic: Genetic Associations and Epidemiology

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: diamond

Funder: National Natural Science Foundation of China