The vitamin D receptor start codon polymorphism (FokI) and bone mineral density in premenopausal American black and white women

J Bone Miner Res. 1997 Jul;12(7):1043-8. doi: 10.1359/jbmr.1997.12.7.1043.


This study examines the association between bone mineral density (BMD) and a start codon polymorphism (SCP) at the translation initiation site of the vitamin D receptor (VDR) gene. The thymine/cytosine (T/C) polymorphism in the first of two start (ATG) codons can be detected by a restriction fragment length polymorphism (RFLP) using the endonuclease FokI, which recognizes ATG as part of its restriction site. F indicates absence of the first ATG and a VDR that is shorter by three amino acids. The FokI genotype was determined in 154 premenopausal American women (72 black and 82 white) who were 20-40 years old. BMD of the total body, femoral neck, and lumbar spine were measured by dual-energy X-ray absorptiometry. The distribution of the SCP genotypes differed significantly by race (p < 0.001): 4% of blacks versus 18% of whites were ff homozygous and 65% of blacks versus 37% of whites were FF homozygous. There was no statistically significant interaction between race and SCP genotype in analyses of BMD at any skeletal site. In the group as a whole, the ff women had femoral neck BMD that was 7.4% lower than that of the FF women. The ff white women had total body BMD values that were 4.3% lower and femoral neck values that were 12.1% lower than FF white women. Total body and femoral neck BMD did not differ significantly by genotype in black women, and spine BMD did not differ by genotype in either race. Addition of the SCP genotype to analysis of covariance models comparing BMD of the black and white women reduced estimated differences in femoral neck BMD between the two groups by about 35%. In conclusion, the SCP polymorphism, detected with the endonuclease FokI, appears to influence peak bone density, particularly at the femoral neck. Racial differences in its distribution may explain some of the racial difference in femoral neck BMD.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • African Continental Ancestry Group / genetics
  • Alleles
  • Bone Density / genetics*
  • Bone Density / physiology
  • Codon, Initiator / genetics*
  • Deoxyribonucleases, Type II Site-Specific
  • European Continental Ancestry Group / genetics
  • Female
  • Femur Neck / metabolism
  • Gene Frequency
  • Genotype
  • Humans
  • Menstruation
  • Polymorphism, Restriction Fragment Length*
  • Receptors, Calcitriol / genetics*
  • United States


  • Codon, Initiator
  • Receptors, Calcitriol
  • endodeoxyribonuclease BsmI
  • endodeoxyribonuclease FokI
  • Deoxyribonucleases, Type II Site-Specific