Exploratory analysis of CaSR gene polymorphisms and haplotypes in relation to urolithiasis in the Qiongnan population of Hainan, China: a small-sample case–control study

Calcium urolithiasis arises from complex interactions between environmental and genetic factors regulating calcium metabolism. The calcium-sensing receptor (CaSR) is essential for maintaining calcium homeostasis, yet population-specific genetic effects remain insufficiently characterized. A case–control study was conducted in the Qiongnan region of Hainan Province, including 50 patients with urolithiasis and 54 matched controls. Five CaSR single-nucleotide polymorphisms (rs7652589, rs6776158, rs1501899, rs1801725, and rs1042636) were genotyped by Sanger sequencing. Genotype–phenotype associations were assessed under multiple inheritance models, and haplotype analyses were performed to evaluate combined variant effects. None of the five CaSR SNPs showed a significant association with urolithiasis after multivariable adjustment. Four major haplotypes were identified, and the AGAGA haplotype was nominally associated with a markedly reduced risk of urolithiasis (adjusted OR = 0.217, 95% CI = 0.054–0.872, P = 0.031). No significant relationship was found between CaSR variants and stone composition. The CaSR AGAGA haplotype showed a nominal association with reduced susceptibility; however, given the limited sample size and low post-hoc power, these findings should be interpreted as exploratory and require validation in larger, independent cohorts.