Abstract
Abstract Previous studies of the vitamin D receptor (VDR) polymorphisms and bone mineral density (BMD) have suggested that there may be differences in calcium absorption among groups of women with different VDR genotypes, and that the association may be stronger in younger women. To investigate the association between the VDR polymorphisms and BMD, this study was undertaken in the Framingham Study Cohort and a group of younger volunteers. Subjects from the Framingham Study (ages 69–90 years) included those who underwent BMD testing and who had genotyping for the VDR alleles (n = 328) using polymerase chain reaction methods and restriction fragment length polymorphisms with BsmI (B absence, b presence of cut site). A group of younger volunteer subjects (ages 18–68) also underwent BMD testing and VDR genotyping (n = 94). In Framingham Cohort subjects with the bb genotype, but not the Bb or BB genotypes, there were significant associations between calcium intake and BMD at five of six skeletal sites, such that BMD was 7–12% higher in those with dietary calcium intakes greater than 800 mg/day compared with those with intakes <500 mg/day. The data also suggested that BMD was higher in persons with the bb genotype only in the group with calcium intakes above 800 mg/day. No significant differences were found in the Framingham Cohort for age-, sex-, and weight-adjusted BMD at any skeletal site between those with the BB genotype and those with the bb genotype regardless of 25-hydroxyvitamin D levels or country of origin. In the younger volunteers, BMD of the femoral neck was 5.4% higher (p < 0.05) in the bb genotype group compared with the BB group and 11% higher (p < 0.05) in males with the bb genotype compared with the BB group. There were no significant differences at the lumbar spine. In this study, the association between calcium intake and BMD appeared to be dependent upon VDR genotype. The finding of an association between dietary calcium intake and BMD only in the bb genotype group suggests that the VDR genotype may play a role in the absorption of dietary calcium. Studies that do not consider calcium intake may not detect associations between VDR genotype and BMD. In addition, the association between VDR alleles and BMD may become less evident in older subjects.
Bibliography
Kiel, D. P., Myers, R. H., Cupples, L. A., Kong, X. F., Zhu, X. H., Ordovas, J., Schaefer, E. J., Felson, D. T., Rush, D., Wilson, P. W. F., Eisman, J. A., & Holick, M. F. (1997). The BsmI Vitamin D Receptor Restriction Fragment Length Polymorphism (bb) Influences the Effect of Calcium Intake on Bone Mineral Density. Journal of Bone and Mineral Research, 12(7), 1049â1057.
Authors
12
- Douglas P. Kiel (first)
- Richard H. Myers (additional)
- L. ADRIENNE Cupples (additional)
- Xiang F. Kong (additional)
- Xue H. Zhu (additional)
- Jose Ordovas (additional)
- Ernest J. Schaefer (additional)
- David T. Felson (additional)
- David Rush (additional)
- Peter W. F. Wilson (additional)
- John A. Eisman (additional)
- Michael F. Holick (additional)
References
28
Referenced
95
10.1038/367284a0
/ Nature / Prediction of bone density from vitamin D receptor alleles by Morrison (1994)10.1172/JCI117568
/ J Clin Invest / Bone mineral density in relation to polymorphism at the vitamin D receptor gene locus by Hustmyer (1994)10.1136/bmj.310.6991.1357
/ Br Med J / Influence of vitamin D receptor genotype on bone mineral density in postmenopausal women: A twin study in Britain by Spector (1995){'key': '2024020713231356800_bib4', 'first-page': '2158', 'article-title': 'Lack of high prevalence of the BB vitamin D receptor genotype in severely osteoporotic women', 'volume': '80', 'author': 'Looney', 'year': '1995', 'journal-title': 'J Clin Endo Metab'}
/ J Clin Endo Metab / Lack of high prevalence of the BB vitamin D receptor genotype in severely osteoporotic women by Looney (1995)10.1016/S0140-6736(94)92297-7
/ Lancet / Vitamin D receptor genotypes in osteoporosis by Melhus (1994)10.1016/S0140-6736(94)91690-X
/ Lancet / Vitamin D receptor gene polymorphism and bone mineral density in healthy Japanese women by Yamagata (1994)10.1016/S0140-6736(95)92019-6
/ Lancet / Vitamin D receptor genotypes and bone mineral density by Kroger (1995)10.1002/jbmr.5650100621
/ J Bone Miner Res / the BsmI vitamin D receptor restriction fragment length polymorphism (BB) predicts low bone density in premenopausal black and white women by Fleet (1995)10.1002/jbmr.5650100622
/ J Bone Miner Res / The contribution of vitamin D receptor gene alleles to the determination of bone mineral density in normal and osteoporotic women by Riggs (1995)10.1002/jbmr.5650100620
/ J Bone Miner Res / Vitamin D receptor alleles and rates of bone loss: Influences of years since menopause and calcium intake by Krall (1995)10.1016/S0140-6736(95)90404-2
/ Lancet / Vitamin-D-receptor-gene polymorphisms and change in lumbar-spine bone mineral density by Ferrari (1995)10.1016/S0140-6736(95)90740-8
/ Lancet / Vitamin-D-receptor-gene polymorphism and bone loss by Keen (1995)10.1002/jbmr.5650100902
/ J Bone Miner Res / Vitamin D receptor gene polymorphisms do not predict bone turnover and bone mass in healthy premenopausal women by Garnero (1995)10.1002/jbmr.5650110718
/ J Bone Miner Res / Vitamin D receptor alleles, bone mineral density and turnover in premenopausal Japanese women by Tokita (1996)10.1002/jbmr.5650110614
/ J Bone Miner Res / Vitamin D receptor gene polymorphisms are not related to bone turnover, rate of bone loss, and bone mass in postmenopausal women: The OFELY Study by Garnero (1996)10.1002/jbmr.5650100903
/ J Bone Miner Res / Vitamin D receptor gene alleles and osteoporosis: An affirmative view by Eisman (1995)10.1002/jbmr.5650100904
/ J. Bone Miner Res / Vitamin D receptor gene alleles and osteoporosis: A contrasting view by Peacock (1995)10.1016/S0140-6736(94)90393-X
/ Lancet / Vitamin D receptor genotypes in osteoporosis by Parfitt (1994)10.1002/jbmr.5650111203
/ J Bone Miner Res / Are vitamin D receptor polymorphisms associated with bone mineral density? A meta-analysis by Cooper (1996){'key': '2024020713231356800_bib20', 'first-page': '3657', 'article-title': 'Calcium absorption on high and low calcium intakes in relation to vitamin D receptor genotype', 'volume': '80', 'author': 'Dawson-Hughes', 'year': '1995', 'journal-title': 'J Clin Endocrinol Metab'}
/ J Clin Endocrinol Metab / Calcium absorption on high and low calcium intakes in relation to vitamin D receptor genotype by Dawson-Hughes (1995)10.1002/jbmr.5650070511
/ J Bone Miner Res / Bone mineral density in elderly men and women: Results form the Framingham osteoporosis study by Hannan (1992)10.1093/oxfordjournals.aje.a114086
/ Am J Epidemiol / Reproducibility and validity of a semiquantitative food frequency questionnaire by Willett (1985)10.1016/0009-8981(74)90241-1
/ Clin Chim Acta / A competitive protein-binding assay for 25-hydroxycholecalciferol and 25-hydroxyergocalciferol in serum by Preece (1974){'key': '2024020713231356800_bib24', 'first-page': '893', 'volume-title': 'SAS/STAT Users Guide. Version 6.09; GLM Procedure', 'author': 'SAS Institute, Inc.', 'year': '1990'}
/ SAS/STAT Users Guide. Version 6.09; GLM Procedure by SAS Institute, Inc. (1990){'key': '2024020713231356800_bib25', 'first-page': '289', 'volume-title': 'Release 6.07; The MIXED Procedure', 'author': 'SAS Institute, Inc.', 'year': '1992'}
/ Release 6.07; The MIXED Procedure by SAS Institute, Inc. (1992)10.1002/jbmr.5650111024
/ J Bone Miner Res / Determinants of premenopausal bone mineral density: The interplay of genetic and lifestyle factors by Salamone (1996)10.1016/S0140-6736(95)92019-6
/ Lancet / Vitamin D receptor genotypes and bone mineral density by Matsuyama (1995){'issue': 'Suppl 1', 'key': '2024020713231356800_bib28', 'first-page': 'S208', 'article-title': 'Differential expression of VDR gene alleles', 'volume': '11', 'author': 'Crofts', 'year': '1996', 'journal-title': 'J Bone Miner Res'}
/ J Bone Miner Res / Differential expression of VDR gene alleles by Crofts (1996)
Dates
Type | When |
---|---|
Created | 19 years, 4 months ago (April 26, 2006, 6:03 p.m.) |
Deposited | 1 year, 5 months ago (March 13, 2024, 10:55 a.m.) |
Indexed | 5 months, 1 week ago (March 27, 2025, 12:15 p.m.) |
Issued | 28 years, 2 months ago (July 1, 1997) |
Published | 28 years, 2 months ago (July 1, 1997) |
Published Online | 15 years, 9 months ago (Dec. 4, 2009) |
Published Print | 28 years, 2 months ago (July 1, 1997) |
@article{Kiel_1997, title={The BsmI Vitamin D Receptor Restriction Fragment Length Polymorphism (bb) Influences the Effect of Calcium Intake on Bone Mineral Density}, volume={12}, ISSN={1523-4681}, url={http://dx.doi.org/10.1359/jbmr.1997.12.7.1049}, DOI={10.1359/jbmr.1997.12.7.1049}, number={7}, journal={Journal of Bone and Mineral Research}, publisher={Oxford University Press (OUP)}, author={Kiel, Douglas P. and Myers, Richard H. and Cupples, L. ADRIENNE and Kong, Xiang F. and Zhu, Xue H. and Ordovas, Jose and Schaefer, Ernest J. and Felson, David T. and Rush, David and Wilson, Peter W. F. and Eisman, John A. and Holick, Michael F.}, year={1997}, month=jul, pages={1049–1057} }