Potential Role of miR-484 in Modulating VDR Gene Expression Level in Calcium Oxalate Kidney Stone Patients

Calcium oxalate (CaOx) kidney stones, accounting for over 70% of all types, are the most common stone type. MicroRNAs (miRNAs) are post-transcriptional epigenetic regulators, involved in disease development. One of these miRNAs is miRNA 484 (miR-484). Vitamin D (VD), a fat-soluble vitamin important for calcium (Ca) metabolism, is primarily mediated by the Vitamin D Receptor (VDR), a nuclear transcription factor. This study aimed to investigate miR-484's regulatory role in modulating VDR gene expression, evaluate serum VD and biochemical parameters in CaOx kidney stone patients compared to healthy controls, and their potential as diagnostic biomarkers. Blood samples were collected from 50 CaOx patients and 40 controls. Serum VD, Ca, urea, and creatinine levels were measured. To assess miR-484 and VDR gene expression, absolute quantification via RT-qPCR was performed. Comparisons, correlations, and ROC curve analyses were performed. The results showed that patients exhibited non-significantly higher serum Ca, urea, and creatinine levels than controls. While VD levels were significantly lower in patients compared to controls. Gene expression analysis revealed a significant miR-484 downregulation and VDR upregulation in patients. Moderate negative correlation was observed between miR-484 and VDR expression in patients. ROC analysis showed that VD, VDR, and miR-484 had good diagnostic accuracy. In conclusion, the study reveals that the downregulation of miR-484 in CaOx patients may lead to overexpression of the VDR, potentially altering VD metabolism and leading to VD deficiency, which can disrupt Ca handling in bone and kidneys, contributing to hypercalciuria, one of the primary risk factors for CaOx stone formation.