Calcium-sensing receptor genetic variants and their association with CKD-MBD in South Indian Tamils.

Abstract

The progressive degradation of the renal parenchyma and reduction of functional nephrons characterise chronic kidney disease (CKD). Disorders of bone mineral metabolism is one of the leading causes of morbidity and mortality in CKD. Calcium-sensing receptor (CASR) allows cells to detect changes in blood calcium levels and regulate its concentration. Hence, we aim to study the relationship between genetic variants of CASR and CKD and their relation with mineral bone disease (MBD). A total of 180 CKD patients and 180 controls were recruited. Bone mineral density of the lumbar spine, hip, and forearm was measured using a dual X-ray absorptiometry (DEXA) scan. Circulating levels of parathyroid hormone (PTH) were measured by ELISA. Genotyping was done by real-time quantitative PCR. A significant difference in the distribution of the GAG haplotype (rs7652589, rs1501899, rs1801725) was observed between CKD patients and controls. Participants with the GT genotype of rs1801725 had lower BMD in the forearm. The TT genotype of rs1801725 was associated with decreased serum calcium levels. A regression model indicated that the GT genotype of rs1801725 and AG and GG genotypes of rs7652589 were significant predictors of forearm BMD. GAG haplotype of CASR SNPs is linked to CKD risk in South Indian Tamils. GT genotype of rs1801725 and AG and GG genotype of rs7652589 are independent predictors of MBD in patients with CKD.