Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Prediction of bone density from vitamin D receptor alleles

A Correction to this article was published on 01 May 1997

Abstract

BONE density achieved in early adulthood is the major determinant of risk of osteoporotic fracture. Up to 60% of women1,2 suffer osteoporotic fractures as a result of low bone density2, which is under strong genetic control3–6 acting through effects on bone turnover7,8. Here we show that common allelic variants in the gene encoding the vitamin D receptor9 can be used to predict differences in bone density, accounting for up to 75% of the total genetic effect on bone density in healthy individuals. The genotype associated with lower bone density was overrepresented in postmenopausal women with bone densities more than 2 standard deviations below values in young normal women. The molecular mechanisms by which bone density is regulated by the vitamin D receptor gene are not certain, although allelic differences in the 3' untranslated region may alter messenger RNA levels. These findings could open new avenues to the development and targeting of prophylactic interventions. It follows that other pathophysiological processes considered to be subject to complex multifactorial genetic regulation may also be modulated by a single gene with pleiotropic transcriptional actions.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Riggs, B. L. & Melton, L. J. New Engl. J. Med. 314, 1676–1686 (1986).

    Article  CAS  Google Scholar 

  2. Nguyen, T. V. et al. Br. Med. J. 307, 1111–1115 (1993).

    Article  CAS  Google Scholar 

  3. Smith, D. M., Nance, W. E., Kang, K. W., Christian, J. C. & Johnston, C. C. Jnr. J. clin. Invest. 52, 2800–2808 (1973).

    Article  CAS  Google Scholar 

  4. Moller, M. et al. Calcif. Tissue Res. 25, 197–201 (1978).

    Article  CAS  Google Scholar 

  5. Pocock, N. A. et al. J. clin. Invest. 80, 706–710 (1987).

    Article  CAS  Google Scholar 

  6. Dequeker, J. et al. Bone 8, 207–209 (1987).

    Article  CAS  Google Scholar 

  7. Seeman, E. et al. New Engl. J. Med. 320, 554–558 (1989).

    Article  CAS  Google Scholar 

  8. Kelly, P. J., Eisman, J. A. & Sambrook, P. N. Osteoporosis Int. 1, 1–5 (1990).

    Article  Google Scholar 

  9. Kelly, P. J. et al. J. clin. Endocrin. Metab. 72, 808–814 (1991).

    Article  CAS  Google Scholar 

  10. Morrison, N. A., Yeoman, R., Kelly, P. J. & Eisman, J. A. Proc. natn. Acad. Sci. U.S.A. 89, 6665–6669 (1992).

    Article  ADS  CAS  Google Scholar 

  11. Pocock, N. A. et al. Med. J. Aust. 146, 293–297 (1987).

    CAS  PubMed  Google Scholar 

  12. Pocock, N. A. et al. J. Bone Min. Res. 3, 601–604 (1988).

    Article  CAS  Google Scholar 

  13. Pocock, N. A., Eisman, J. A., Yeates, M. G., Sambrook, P. N. & Eberl, S. J. clin. Invest. 78, 618–621 (1986).

    Article  CAS  Google Scholar 

  14. Pocock, N. A. et al. J. Bone Min. Res. 4, 441–448 (1989).

    Article  CAS  Google Scholar 

  15. Haseman, J. K. & Elston, R. C. Behavl Genet. 1, 11–19 (1970)

    Article  CAS  Google Scholar 

  16. Haseman, J. K. & Elston, R. C. Behavl Genet. 2, 3–19 (1972).

    Article  CAS  Google Scholar 

  17. Morrison, N. A. et al. Science 246, 1158–1161 (1989).

    Article  ADS  CAS  Google Scholar 

  18. Demay, M. B., Roth, D. A. & Kronenberg, H. M. J. biol. Chem. 264, 2279–2282 (1989).

    CAS  PubMed  Google Scholar 

  19. Kerner, S. A., Scott, R. A. & Pike, J. W. Proc. natn. Acad. Sci. U.S.A. 86, 4455–4459 (1989).

    Article  ADS  CAS  Google Scholar 

  20. Bell, N. H. et al. J. clin. Invest. 76, 470–473 (1985).

    Article  CAS  Google Scholar 

  21. Arveiler, B., Petkovich, M., Mandel, J. L. & Chambon, P. Nucleic Acids Res. 16, 6252 (1988).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Morrison, N., Qi, J., Tokita, A. et al. Prediction of bone density from vitamin D receptor alleles. Nature 367, 284–287 (1994). https://doi.org/10.1038/367284a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/367284a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing