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

Vitamin D [1,25(OH)(2)D-3] 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% BE, 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 less than or equal to 0.04). The i-OC concentrations in the aa group was also approximately double those in both the AA group and Aa group (P less than or equal to 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.