GSTO1 as a Potential Risk Factor for Diabetic Nephropathy: Evidence From M endelian Randomisation and Multi‐Omics Analyses

AIM: Diabetic nephropathy (DN) is a major complication of diabetes mellitus and a leading cause of end-stage renal disease (ESRD). Glutathione S-transferase omega 1 (GSTO1) is implicated in redox regulation and inflammation, but its causal role in DN remains unclear. This study aimed to investigate the potential causal relationship between GSTO1 and DN risk. METHODS: Two-sample Mendelian randomisation (MR) analysis was performed to assess the causal association between genetic variants of GSTO1 and DN. Expression analyses were conducted using the Nephroseq database, GEO datasets, and single-cell RNA sequencing (scRNA-seq). Additionally, GSTO1 expression was examined in HK-2 cells treated with high glucose. RESULTS: MR analysis revealed that genetic variants of GSTO1 were significantly associated with an increased risk of DN. Nephroseq and GEO data showed elevated GSTO1 expression in DN samples. ScRNA-seq demonstrated increased GSTO1 expression in proximal tubular cells of diabetic patients. Consistently, high-glucose treated HK-2 cells exhibited upregulated GSTO1 expression. CONCLUSION: These findings suggest preliminary evidence for a potential causal association between GSTO1 and DN, suggesting that GSTO1 may play an important role in DN pathogenesis. GSTO1 could serve as a potential molecular marker and therapeutic target for DN.