Abstract
Background Nephrolithiasis, commonly known as kidney stone disease (KSD), is a multi-factorial disorder influenced by genetic and metabolic factors. The calcium-sensing receptor (CASR) plays a crucial role in calcium homeostasis, and single-nucleotide polymorphisms (SNPs) in the CASR gene may contribute to the occurrence and recurrence of nephrolithiasis. This study investigates the association of CASR SNPs (rs1801725, rs1042636, and rs1501899) with KSD in the Indian population. Methods A single Institute case-control study was conducted between May 2022 and May 2024, including 110 KSD patients and 100 healthy controls. Genotyping of CASR polymorphisms was performed using TaqMan®SNP Genotyping Assay. The association between SNPs and KSD risk was evaluated using odds ratios. Results The T allele of SNP rs1801725 and the G allele of SNP rs1042636 were significantly associated with an increased risk of KSD (P < 0.0001) and were linked to hypercalcemia and hypercalciuria. The A allele of SNP rs1501899 showed a weaker, non-significant association with KSD (P = 0.0767). The G allele of SNP rs1042636 showed a potential trend toward increased risk of recurrent stone formation (OR = 1.87, p = 0.113). Conclusion Our findings suggest that CASR polymorphisms rs1801725 and rs1042636 contribute to KSD susceptibility in the Indian population, influencing calcium metabolism. Genetic screening for these SNPs may aid in early detection and personalized management of KSD patients, particularly those at risk for recurrent stones.