Single-Nucleotide Polymorphism (SNP) A986S (rs1801725) of the Calcium-Sensing Receptor in Children With Idiopathic Hypercalciuria

Background Idiopathic hypercalciuria (IH) is a common metabolic abnormality in children and an important risk factor for hematuria, nephrolithiasis, and recurrent urinary symptoms. Genetic factors, particularly variations in the calcium-sensing receptor (CaSR) gene, may predispose individuals to altered calcium homeostasis. The CaSR A986S polymorphism (rs1801725) has been implicated in abnormal calcium metabolism and stone disease, but evidence in pediatric populations remains limited. Objective To investigate the association between the CaSR A986S (rs1801725) polymorphism and IH in children. Methods A case-control study was conducted at a tertiary nephrology center in Bangalore between January 2022 and May 2023. Sixty children aged 4-14 years with IH were compared with 60 age- and sex-matched controls. Clinical characteristics, serum calcium levels, and 24-hour urinary calcium excretion were assessed. Genotyping for rs1801725 (A986S) was performed, and genotype frequencies, p-values, and ORs were calculated using SPSS software. Results Children with IH had significantly higher 24-hour urinary calcium excretion than controls (413 ± 76 vs 215 ± 132 mg/day; p = 0.001). The mutant TT genotype was more frequent in patients with IH than in controls (15% vs 1.7%; p = 0.02), while the normal GG genotype was significantly less common in patients with IH (60% vs 91%; p = 0.0002). Allelic analysis showed a significantly higher frequency of the T allele in patients with IH (35% vs 5%), conferring a markedly increased risk of IH (OR = 10.23; 95% CI: 2.85-36.66; p = 0.0004). Conclusion The CaSR A986S (rs1801725) polymorphism is significantly associated with IH in children. The T allele, particularly the TT and GT genotypes, confers a markedly increased risk of IH, suggesting a meaningful genetic contribution to calcium dysregulation in the pediatric population. These findings support the potential role of CaSR genotyping in early risk stratification and individualized management of IH.