BsmlPolymorphism of the Vitamin D Receptor Gene in Hyperparathyroid or Hypoparathyroid Dialysis Patients

Abstract

A b s t r a c t Since bone mineral density may be influenced by the polymorphisms of the vitamin D receptor (VDR JgeneBone mineral density is influenced by environmental factors, such as dietary calcium intake and physical activity, and by genetic determinants. Since vitamin D is important in calcium metabolism and bone turnover, it has been suggested that polymorphisms for the vitamin D receptor (VDR) gene may be one of these factors. In a large population of healthy whites, Morrison and coworkers 1 -2 described an association between the VDR-BB genotype and higher levels of osteocalcin, an index of bone turnover. They also found that postmenopausal women with the BB genotype had low bone mineral density in the lumbar spine and femoral neck, resulting in a lower fracture threshold. They suggested that the presence of the B allele of the VDR gene influenced the bone turnover and, therefore, could be considered a genetic marker of osteoporosis. Although the specific molecular role was not described fully, they suggested that the B allele might be associated with increased transcriptional activity of the VDR gene and prolonged messenger RNA (mRNA) stability. These results were not confirmed fully in further studies, 3^ probably because of differences in sample size and ethnic background of the populations.Vitamin D works at different sites, including the intestine, kidney, bone, and parathyroid glands 78 ; in these sites, calcitriol interacts with the nuclear VDR, causing inhibition of the parathyroid hormone gene transcription and up-regulation of the VDR itself. In renal failure, the long-term phosphorus retention and the reduced vitamin D production induce secondary hyperparathyroidism, which includes elevated serum parathyroid hormone (PTH) levels, calcium-phosphorus balance alterations, and high bone turnover osteodystrophy, the so-called osteitis fibrosa (OF). 9 However, an increasing number of patients undergoing dialysis have been seen with low levels of circulating PTH (hypoparathyroidism) and abnormalities of bone remodeling, leading to low turnover osteodystrophy, named aplastic bone disease (ABD). The biochemical 3 6 6 Am J Clin Pathol 1999;112:366-370

Profile of vitamin D receptor polymorphism Bsm I and FokI in end stage renal disease Egyptian patients on maintenance hemodialysis

“…Similarly, Tagliabue et al [48], reported a higher frequency of BB variant among Italian dialysis patients with hypoparathyroidism compared to patients with secondary hyperparathyroidism (34% versus 16%). Also, a protective effect of the B allele has been reported in Japanese patients undergoing hemodialysis [49].…”

The influence of BsmI and TaqI vitamin D receptor gene polymorphisms on the intensity of hyperparathyroidism in Iranian hemodialysis patients

“…[14] Also in our study the frequency of BB genotype is higher in groups III (300 ≥ iPTH < 600 pg/mL) and IV (iPTH ≥ 600 pg/mL) thus BB genotype may develop more severe secondary hyperparathyroidism but the relationship between BsmI variants and serum iPTH level was not statistically significant. Tagliabue et al .,[15] in their study concluded that patients with the B allele and BB genotype had a significantly lower serum PTH and alkaline phosphatase levels than patients with the b allele and bb genotype but the difference did not reach statistical significance. In our study, the calcium level seen in the BB genotype is less than those for Bb and bb genotypes ( P = 0.002).…”

Vitamin D Receptor Gene Polymorphism and Left Ventricular Hypertrophy in Chronic Kidney Disease

“…Indeed, most studies have been aimed at determining whether VDR polymorphisms could be involved in the development of secondary hyperparathyroidism (sHPT), one of the main complications in patients with CKD. Interestingly, the VDR BsmI b allele was shown to have a higher incidence in HD patients with sHPT and drive the progression toward sHPT in patients with ESRD, since BB individuals had lower levels of PTH and higher calcitriol levels than bb individuals in every stage of CKD [13,14,15,16,17]. Serum PTH levels in CKD patients were also affected by FokI polymorphism, since patients in the FF group had significantly higher PTH levels than those in both the Ff and ff groups, while no significant differences in serum levels of calcidiol or calcium were found among genotypes [18].…”