Apa I polymorphism in the vitamin D receptor gene may affect the parathyroid response in Japanese with end-stage renal disease

Abstract

Vitamin D [1,25(OH)2D3] plays a key role in the pathogenesis of secondary hyperparathyroidism. A polymorphism in the vitamin D receptor (VDR) gene is reported to be involved in bone mineral density and the serum level of intact-osteocalcin (i-OC) in patients with osteoporosis. We investigated the relationship between VDR gene polymorphisms and the levels of intact PTH (i-PTH) and i-OC in 129 Japanese patients with end-stage renal disease (ESRD). The VDR gene sequences were PCR-amplified, and the product was cleaved with the restriction enzymes Bsm I and Apa I. Undigested alleles were designated as B and A, and the digested alleles as b and a, respectively. The frequencies for the Bsm I polymorphism were 0.0% BB, 19.4% Bb, and 80.6% bb, while those for Apa I polymorphism were 14.2% AA, 47.2% Aa, and 38.6% aa. The Bsm I polymorphism of VDR was greatly biased in Japanese people. The i-PTH level in the aa group was about twice as high as those in the both AA group and Aa group (P < or = 0.04). The i-OC concentrations in the aa group was also approximately double those in both the AA group and Aa group (P < or = 0.03). In contrast, no significant differences in age, duration of dialysis, male/female ratio, or the incidence of diabetic nephropathy were observed among these three groups. On the other hand, there was no significant differences in i-PTH and i-OC between the Bb and bb groups. These results suggest that VDR gene polymorphisms can affect parathyroid response in ESRD patients, and the Apa I polymorphism is more informative in Japanese patients than the Bsm I polymorphism. The VDR a gene allele may define the pathogenesis of secondary hyperparathyroidism and of high turnover bone disease in patients with ESRD.

Association of vitamin D receptor gene polymorphisms with end-stage renal disease and the development of high-turnover renal osteodystrophy in a Chinese population

“…The association of the ApaI polymorphism in the VDR gene with bone and mineral metabolism has been investigated in hemodialysis patients. Yokoyama et al (1998) reported that serum PTH and osteocalcin levels among patients with the CC genotype were almost twice as high as in patients carrying the A allele. Consistent with their results, our study revealed that the C allele of the ApaI polymorphism is significantly associated with ESRD risk.…”

Vitamin D Receptor Gene Polymorphism Detected by Digestion with Apa I Influences the Parathyroid Response to Extracellular Calcium in Japanese Chronic Dialysis Patients

“…In all subjects, genomic DNA was extracted from peripheral leukocytes. The polymerase chain reaction products were digested at the intron between exon 8 and exon 9 with restriction enzyme Apa I, using two primers that recognized 740 base pairs of the VDR gene [11]. …”

“…There have been some reports on the relationship between VDR gene polymorphism and bone mineral metabolism in osteoporosis patients [6, 7, 8]. Recently, there have also been reports on the relationship between VDR polymorphism and parathyroid hormone (PTH) as well as bone mineral density in ESRD patients subjected to renal replacement therapy [9, 10, 11, 12, 13]. We have previously indicated the possibility of the influence of Apa I fragment length polymorphism of the VDR gene on onset and progression of secondary hyperparathyroidism in Japanese ESRD patients [11].…”

“…Recently, there have also been reports on the relationship between VDR polymorphism and parathyroid hormone (PTH) as well as bone mineral density in ESRD patients subjected to renal replacement therapy [9, 10, 11, 12, 13]. We have previously indicated the possibility of the influence of Apa I fragment length polymorphism of the VDR gene on onset and progression of secondary hyperparathyroidism in Japanese ESRD patients [11]. In this study, we investigated whether VDR gene polymorphism, as detected by Apa I, is associated with parathyroid responsiveness to changes in extracellular Ca 2+ concentration.…”

Vitamin D Receptor (Vdr) Gene Polymorphism and Maternal Vitamin D Deficiency in Indian Women With Preterm Birth (Ptb)

“…Several polymorphic sites have been described within VDR gene. Polymorphism near the 3' end of VDR gene identified by restriction enzyme BsmI, TaqI, ApaI, and FokI associated with osteoporosis [17], Type 1 diabetes mellitus [18], polycystic ovary syndrome [19], end-stage renal disease [20], several types of carcinoma such as breast, prostate, and colon carcinoma [21]. Therefore, genetic disparities of prematurity with regards to VDR gene polymorphism need to be investigated.…”