Objective: Comprehensive sequencing of the coding exons of the calcium-sensing receptor gene (CASR) was performed in a group of Iranian recurrent calcium kidney stone-formers and the results were compared with a control group.
Material and methods: Serum and urine parameters were evaluated in 99 males aged between 30 and 55 years old with idiopathic recurrent calcium urolithiasis and in 107 men as a control group. Products of polymerase chain reaction were sequenced using forward primer until a mutation was found in that exon. Then, other cases were analysed by single-strand conformation polymorphism.
Results: Four polymorphisms were detected in CASR exons, all in the coding region of exon 7. These polymorphisms and their minor allele frequency were P748P (100%), A986S (1%), R990G (3%) and E1011Q (98%). There was a significantly higher count of 986S (p = 0.006), 990G (p = 0.006) and E1011 (p = 0.02) alleles in patients. The odds ratio (95% confidence interval) was 2.55 (1.31-4.96) in those at risk of stone disease for the 986S allele and 8.06 (1.80-35.9) for the 990G allele. Men with the RR genotype at R990G showed a significantly higher serum ionized calcium than the RG or GG group (p = 0.03). A significantly lower serum total calcium was found in subjects with the QQ than the EQ genotype with respect to the 1011 locus (p = 0.005). Furthermore, the 1011Q allele was marginally associated with hypercalciuria (p = 0.05).
Conclusion: The 986S, 990G and 1011Q alleles were associated with a recurrent calcium kidney stone-forming state. 986S and 1011Q alleles, but not 986S, were associated with hypercalcaemia.