Priyadarshini G, Dhinesh A, Parameswaran Sreejith, Sahoo Jayaprakash, Selvarajan Sandhiya, Rajappa Medha
Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, 605006, India.
Department of Nephrology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
J Appl Genet. 2025 Mar 14. doi: 10.1007/s13353-025-00955-7.
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.
肾实质的进行性退化和功能性肾单位的减少是慢性肾脏病（CKD）的特征。骨矿物质代谢紊乱是CKD发病和死亡的主要原因之一。钙敏感受体（CASR）使细胞能够检测血钙水平的变化并调节其浓度。因此，我们旨在研究CASR基因变异与CKD之间的关系及其与矿物质骨病（MBD）的关系。共招募了180例CKD患者和180名对照。使用双能X线吸收法（DEXA）扫描测量腰椎、髋部和前臂的骨密度。通过酶联免疫吸附测定（ELISA）测量甲状旁腺激素（PTH）的循环水平。通过实时定量PCR进行基因分型。在CKD患者和对照之间观察到GAG单倍型（rs7652589、rs1501899、rs1801725）分布的显著差异。rs1801725的GT基因型参与者的前臂骨密度较低。rs1801725的TT基因型与血清钙水平降低有关。回归模型表明，rs1801725的GT基因型以及rs7652589的AG和GG基因型是前臂骨密度的重要预测指标。CASR单核苷酸多态性的GAG单倍型与南印度泰米尔人的CKD风险相关。rs1801725的GT基因型以及rs7652589的AG和GG基因型是CKD患者MBD的独立预测指标。
