Association of Calcium Sensing Receptor Gene Polymorphism(rs3804594) With Parathyroid hormone levels in Patients With Urinary Calcium Oxalate Stones:A Cross-sectional Study

Abstract

Background: Calcium oxalate nephrolithiasis may be considered as a complex disease having multiple pathogenetic mechanisms. Calcium homeostasis is crucially regulated by the calcium sensing receptor(CaSR) expressed mainly in PTH glands , which reduces passive and active calcium reabsorption in distal tubules, and hence a candidate gene for calcium nephrolithiasis. Objective of the study was to determine the association of CaSR gene polymorphism(rs3804594)  with calcium oxalate stone formation  and also to  assess  the  association  between  CaSR  gene  polymorphism  and  serum  levels of PTH  in patients with urinary oxalate  stones.

Methodology: Two Hundred subjects were recruited in the cross-sectional study,out of which  100 were patients with calcium oxalate stones  & 100 were healthy controls. Analysis of the Single Nucleotide Polymorphism of CaSR was performed with Polymerase Chain Reaction-Restriction Fragment Length Polymorphism(PCR–RFLP).Chisquare test was applied for the analysis of associations using Graph pad prism.

Results: The genotype frequencies of the cases and controls were in accordance with the Hardy–Weinberg equilibrium with no significant difference in the expected and observed allele frequencies (chi square 4.73, p=0.73). There was no significant association between the CaSR gene polymorphisms and renal stone disease (chi square 0.32,p=0.57) with Odd’s Ratio=1.174. Frequencies of CC (wild) and CT+TT (mutant) genotypes were 47% and 42% in normal serum PTH group, 4% and 7% in patients with elevated serum PTH group. No significant association was observed between the gene polymorphisms and serum PTH levels. Haplotype analysis shows that C allele  is the risk allele that seems to have a dominant genetic effect over the T allele.

Conclusion: It could be concluded from the study there was no significant association between CaSR gene polymorphism with oxalate stone disease. CaSR  gene  polymorphism  was insignificantly associated with the  serum  levels of PTH  in patients with urinary oxalate  stones. However the polymorphism of the calcium-sensing receptor (CaSR) can impact kidney stone formation by altering the receptor's sensitivity to calcium, potentially leading to increased urinary calcium levels and an increased risk of stone development.