Haplotype of CaSR gene is associated with risk of renal stone disease in West Indian population

Abstract

Calcium is the most abundant metabolite involved in the stone matrix. The CaSR gene controls calcium homeostasis, and genetic variation in the CaSR gene could lead to the development of renal stone disease. Therefore, the current study has been designed to assess the association of genetic variants of CaSR gene polymorphisms with renal stone disease. MethodA single-centric prospective study has been carried out on a total of 300 participants (150 cases and 150 controls). Serum levels of calcium, creatinine, parathyroid hormone, and 24 Hour urine metabolites were measured. Two polymorphisms, rs1801725 and rs1042636, of the CaSR gene, have been genotyped for each participant. T-test, Chi-square, and Receiving Operative Curve (ROC) curve analysis were used for statistical analysis. ResultRenal stone patients had signi cantly higher levels of serum parathyroid hormone, creatinine, and 24hr urine metabolites in comparison to the controls. CaSR gene variants rs1801725 (GG) and rs1042636 (AA) both have shown signi cant association with renal stone disease. In addition, individuals having speci c genotypes along with metabolic abnormalities such as hypercalcemia, and hyperparathyroidism are found to be at a higher signi cant risk of developing the renal stone disease. Further, ROC analysis also showed a higher risk (54%) for individuals carrying the GG/AA haplotype. ConclusionIn the present study, the haplotype of the CaSR gene has shown an association with renal stone disease. Individuals with hyperparathyroidism and hypercalcemia and risk genotype have a higher susceptibility to developing the renal stone disease.

The role of the calcium-sensing receptor in the regulation of parathyroid hormone secretion in physiology and in calcitropic diseases

“…Однако полиморфизмы гена CaSR способны привести к гиперкальциурии в сочетании с нефролитиазом. Так, полиморфизм Arg990Gly (замена глицина в позиции 990 на аргинин), а также полиморфизмы rs1042636 (АА), rs1801725 (GG) и rs6776158 (AG) встречаются у пациентов с мочекаменной болезнью [46][47][48][49].…”