Study of The Polymorphism BsmI and TaqI in Vitamin D Receptor Gene in Egyptian Patients With Chronic Kidney Disease

Abstract

Abstract Background Chronic kidney disease (CKD) is a major public health problem and a leading cause of morbidity and mortality worldwide. Chronic kidney disease mineral and bone disorders (CKD-MBD) is a common complication of CKD and an important cause of morbidity and decreased quality of life. Serum levels of 25-hydroxy vitamin D and parathyroid hormone (PTH) provide an accurate picture of bone turnover and mineralization states therefore they could be used with other serum bone biomarkers as non-invasive sensitive bone markers to help management of MBD in CKD. Due to the complex role played by vitamin D in kidney disease, the genotyping for vitamin D receptor (VDR) variants in CKD patients has been regarded as a way for improving the management of the disease. Objective The aim of the present work was to study the association of vitamin D receptor gene polymorphisms BsmI and TaqI with the chronic kidney disease and to assess its relationship with development and progression of chronic kidney disease-mineral bone disease. Subjects and Methods The study was conducted on 60 CKD-MBD patients in addition to 30 age- and sex- matched subjects serving as a healthy control group. Patients were subdivided into two subgroups according to the stage of CKD: subgroup 1a; 30 patients with CKD-MBD under conservative management (stages: 3 and 4 CKD) and subgroup 1b; 30 CKD-MBD patients with end-stage CKD on regular hemodialysis. Determination of BsmI (rs1544410, A>G) and TaqI (rs731236, C>T) polymorphisms of VDR gene was carried out using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). Results The result of the present study revealed that VDR BsmI (rs1544410) gene polymorphism and alleles (Bb, bb) were not associated with susceptibility to the CKD or development and progression of CKD-MBD in the studied CKD-MBD patients. However, having the gene variants of VDR TaqI (rs731236) tt homotypic genotype increased the susceptibility to CKD-MBD compared to having the gene variant TT wild genotype and Tt heterotypic genotype. Moreover, VDR polymorphisms were associated with the mineral status in CKD-MBD Egyptian patients. The VDR BsmI wild (BB) genotypes and the VDR TaqI homotypic (tt) variant were found to be associated with development of severe secondary hyperparathyroidism, hypocalcemia and vitamin D deficiency in the studied Egyptian patients with CKD-MBD. Conclusion VDR BsmI gene polymorphism failed to prove any association with susceptibility to the CKD or development and progression of CKD-MBD. However, VDR TaqI tt homotypic genotype increased the susceptibility to CKD-MBD and progression toward severe secondary hyperparathyroidism, hypocalcemia and vitamin D deficiency.