A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanese women

J Bone Miner Res. 1997 Jun;12(6):915-21. doi: 10.1359/jbmr.1997.12.6.915.


The effect of a T-C transition polymorphism at the translation initiation codon of the human vitamin D receptor (VDR) gene on the biological function of the encoded protein was investigated. Of 239 Japanese women volunteers subjected to genotype analysis for this polymorphism, 32 (13%) were genotype MM (the M allele is ATG at the putative translation start site), 75 (31%) were genotype mm (the m allele is ACG at the putative translation start site), and 132 (55%) were genotype Mm. The bone mineral density (BMD) in the lumbar spine (L2-L4) was determined for 110 healthy premenopausal women from the volunteers and was shown to be 12.0% greater (p < 0.05) for mm homozygotes than for MM homozygotes. Synthesis of the proteins by the M and m alleles from the cloned cDNAs in vitro and in transfected COS-7 cells revealed them to have a size of 50 and 49.5 kD, respectively, as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. This size difference is consistent with initiation of translation of the M allele-encoded protein from an ATG codon located at nucleotides +10 to +12 in the conventional open reading frame. The extent of vitamin D-dependent transcriptional activation of a reporter construct under the control of a vitamin D response element in transfected HeLa cells was approximately 1.7-fold greater for the m type VDR than for the M type protein. These results suggest that the polymorphism at the translation start site of the VDR gene may modulate BMD in premenopausal Japanese women.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Animals
  • Base Sequence
  • Bone Density / genetics*
  • COS Cells
  • Codon, Initiator / genetics
  • DNA / genetics
  • Exons
  • Female
  • Gene Frequency
  • Genotype
  • HeLa Cells
  • Humans
  • Japan
  • Middle Aged
  • Molecular Sequence Data
  • Polymorphism, Genetic*
  • Receptors, Calcitriol / genetics*
  • Receptors, Calcitriol / metabolism*
  • Transfection


  • Codon, Initiator
  • Receptors, Calcitriol
  • DNA