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Vitamin D-binding protein gene microsatellite polymorphism influences BMD and risk of fractures in men

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Abstract

Summary

Here we report the results of a vitamin D-binding protein gene microsatellite polymorphism study in 170 men, comprising healthy male subjects and men with osteoporosis-related symptomatic vertebral fractures. We confirm the results of an earlier study in a different cohort, showing relationship between certain genotypes of (TAAAn)-Alu repeats and reduced BMD and vertebral fractures.

Introduction

Vitamin D-binding protein (DBP) plays a critical role in the transport and metabolism of metabolites of vitamin D, including the key calciotropic hormone 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3).

Methods

We have investigated intra-intronic variable tandem (TAAA)n-Alu repeat expansion in the DBP gene in 170 men, comprising healthy male subjects and men with idiopathic osteoporosis and low trauma fractures.

Results and conclusions

The predominant DBP-Alu genotype in the control subjects was 10/10 (frequency 0.421), whereas the frequency of this genotype in men with osteoporosis was 0.089. DBP-Alu alleles *10, *8 and *9, respectively, were the three commonest in both healthy subjects and men with osteoporosis. Allele *10 was associated with a lower risk of osteoporosis (OR 0.39, 95% CI 0.25–0.64; p < 0.0005), as was allele *11 (odds ratio 0.09, 95% CI 0.01–0.67; p < 0.007). Logistic regression gave similar results, showing that individuals with genotype 10/10 and 19–20 repeats (genotypes 9/10, 9/11, 10/10,) are protected from fracture or osteoporosis. Overall, there was a relationship between DBP Alu genotype and BMD, suggesting that DBP-Alu genotype may influence fracture risk. This effect may be mediated by changes in the circulating concentrations of DBP which influences free concentrations of vitamin D.

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Abbreviations

DBP:

Vitamin D-binding protein

BMD:

Bone mineral density

25(OH)D:

25α-hydroxyvitamin D3

1,25(OH)2D3 :

1α,25-dihydroxyvitamin D3

BMI:

Body mass index

STR:

Short tandem repeats

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Acknowledgements

This work was supported by the National Osteoporosis Society and Newcastle Hospital Special Trustees (HKD and RMF), and the EU project ‘Osteogene’ (No. FP6-502491) (HKD).

Author information

Authors and Affiliations

  1. School of Clinical & Laboratory Sciences, The Medical School, University of Newcastle, Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK

    Z. H. Al-oanzi, D. B. Cook & H. K. Datta

  2. School of Medical Sciences, The Medical School, University of Newcastle, Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK

    S. P. Tuck & R. M. Francis

  3. Department of Human Sciences, Loughborough University, Loughborough, LE11 3TU, UK

    S. S. Mastana

  4. Department of Rheumatology, Derbyshire Royal Infirmary, London Road, Derby, DE1 2QY, UK

    G. D. Summers

Authors
  1. Z. H. Al-oanzi
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  2. S. P. Tuck
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  3. S. S. Mastana
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  4. G. D. Summers
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  5. D. B. Cook
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  6. R. M. Francis
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  7. H. K. Datta
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Corresponding author

Correspondence to H. K. Datta.

Additional information

Funding sources: FP6 (EU), National Osteoporosis Society (U.K); Newcastle University Hospitals Special Trustees.

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Al-oanzi, Z.H., Tuck, S.P., Mastana, S.S. et al. Vitamin D-binding protein gene microsatellite polymorphism influences BMD and risk of fractures in men. Osteoporos Int 19, 951–960 (2008). https://doi.org/10.1007/s00198-007-0516-8

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  • DOI: https://doi.org/10.1007/s00198-007-0516-8

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