A large-scale population-based study of the association of vitamin D receptor gene polymorphisms with bone mineral density

Authors

  • Dr. André G. Uitterlinden,

    Corresponding author
    1. Department of Internal Medicine III, Erasmus University Medical School, Rotterdam, The Netherlands
    • Department of Internal Medicine III FGG-EUR Medical Faculty Erasmus University Rotterdam P.O. Box 1738 3000 DR Rotterdam, The Netherlands
    Search for more papers by this author
  • Huibert A. P. Pols,

    1. Department of Internal Medicine III, Erasmus University Medical School, Rotterdam, The Netherlands
    2. Department of Epidemiology & Biostatistics, Erasmus University Medical School, Rotterdam, The Netherlands
    Search for more papers by this author
  • Huibert Burger,

    1. Department of Epidemiology & Biostatistics, Erasmus University Medical School, Rotterdam, The Netherlands
    Search for more papers by this author
  • Qiuju Huang,

    1. Department of Epidemiology & Biostatistics, Erasmus University Medical School, Rotterdam, The Netherlands
    Search for more papers by this author
  • Paul L. A. van Daele,

    1. Department of Internal Medicine III, Erasmus University Medical School, Rotterdam, The Netherlands
    Search for more papers by this author
  • Cornelia M. van Duijn,

    1. Department of Epidemiology & Biostatistics, Erasmus University Medical School, Rotterdam, The Netherlands
    Search for more papers by this author
  • Albert Hofman,

    1. Department of Epidemiology & Biostatistics, Erasmus University Medical School, Rotterdam, The Netherlands
    Search for more papers by this author
  • Jan C. Birkenhäger,

    1. Department of Internal Medicine III, Erasmus University Medical School, Rotterdam, The Netherlands
    Search for more papers by this author
  • Johannes P. T. M. van Leeuwen

    1. Department of Internal Medicine III, Erasmus University Medical School, Rotterdam, The Netherlands
    Search for more papers by this author

  • Parts of this work were presented as an abstract at the XXIVth European Symposium on Calcified Tissues on May 27–30, 1995, in Aarhus, Denmark, and at the 17th annual meeting of the American Society for Bone and Mineral Research on September 9–13, 1995, in Baltimore, Maryland, U.S.A.

Abstract

Conflicting results have been reported on the association between restriction fragment length polymorphisms (RFLPs) at the vitamin D receptor (VDR) gene locus (i.e., for BsmI, ApaI, and TaqI) and bone mineral density (BMD). We analyzed this association in a large population-based sample (n = 1782) of men and women aged 55–80 years using a novel direct haplotyping polymerase chain reaction (PCR) test to monitor the three polymorphic sites simultaneously. The direct haplotyping test we developed demonstrated a larger degree of genetic polymorphism at the VDR gene locus than described until now. None of the individual RFLPs were associated with BMD at the proximal femur. By analyzing allele dose effects, we identified a VDR haplotype allele weakly associated with low BMD. This allele, as one representative of the group of b alleles, is different from the BsmI allele previously reported by other groups to be associated with low BMD. This suggests allelic heterogeneity at the VDR locus in relation to BMD. Our results indicate at most a small effect of the VDR genotype on BMD in this elderly population. Since anonymous polymorphisms were analyzed, alternative explanations for our results include linkage to another nearby bone-metabolism related gene.

Ancillary