The Association of Calcium- Sensing Receptor (CaSR) Gene Polymorphism and the Risk of Kidney Stone Disease

Abstract

     Urolithiasis or kidney stone is a multiple factorial disorder caused by a complex interaction of genetic predisposition, lifestyle, and dietary habits that lead to the formation of kidney stones. Calcium stones, including calcium oxalate and phosphate, are the most common kidney stones. The calcium-sensing receptor (CaSR) is a protein containing 1078 amino- acids that potentially affects calcium homeostasis and stones formation. Since most stones are calcium-dependent, this represents a starting point for research into calcium status and the genetic polymorphisms affecting it. We investigated the association of the Single nucleotide polymorphisms (SNPs) of the calcium-sensing receptor gene (CaSR), such as rs1801725 A986S and rs1042636 R990G SNPs in the Iraqi kidney stones population. This study included (96) samples, 64 patients with kidney stones, and the control group consisted of 32 healthy individuals. A polymerase chain reaction technique and DNA sequencing were used for genotyping CaSR SNPs. It was found that CaSR rs1801725 GG genotypes (OR 1.0000, 95% CI 0.4273-2.340) have no effect on the disease compared with GT genotypes (OR 1.053, 95% CI 0.4533-2.5035) which is related with disease. CaSR rs 1042636 AA genotypes (OR 1.9676, 95% CI 0.5936-6.5217) are related to disease. Compared with AG genotypes (OR 0.7855, 95% CI 0.2346-2.6303), which reduces the chance of disease.

The results: it was found that CaSR rs1801725 A986S, GG genotype (OR1.0000, 95% CI 0.4273-2.3405) has no effect on the disease compared with GT genotype ( OR 1.053, 95% CI 0.4553- 2.5035), which is associated with increased disease risk compared with the TT genotype ( OR 0.8192, 95% CI 1.830-3.6671). CaSR rs 1042636 R990G, AA genotype (OR 1.9676, 95%CI 0.5936-6.5217) are associated with increased disease risk. The AG genotype (OR 0.7855, 95% CI 0.2346-2.6303) was found to be associated with reducing the chance of the disease. The absence of a GG genotype may be considered a protective genotype.