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

Kidney Int. 1998 Feb;53(2):454-8. doi: 10.1046/j.1523-1755.1998.00781.x.


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.

MeSH terms

  • Alleles
  • Female
  • Genotype
  • Humans
  • Introns / genetics
  • Japan
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / genetics*
  • Kidney Failure, Chronic / physiopathology*
  • Male
  • Middle Aged
  • Osteocalcin / blood
  • Parathyroid Glands / physiopathology*
  • Parathyroid Hormone / blood
  • Polymorphism, Genetic*
  • Receptors, Calcitriol / genetics*


  • Parathyroid Hormone
  • Receptors, Calcitriol
  • Osteocalcin