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Polymorphisms and haplotypes across the osteoprotegerin gene associated with bone mineral density and osteoporotic fractures

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Abstract

Summary

Osteoprotegerin plays a key role in bone remodelling. We studied the association between 24 polymorphisms and haplotypes on the OPG gene and bone mineral density and fractures. After multiple-testing correction, one SNP and two block-haplotypes were significantly associated with FN BMD. Two other block-haplotypes were associated with fracture.

Introduction and Hypothesis

Osteoprotegerin (OPG) plays a key role in bone remodelling. Here we studied the association between polymorphisms and haplotypes on the OPG gene and bone mineral density (BMD) and fractures.

Methods

Twenty-four single nucleotide polymorphisms (SNPs) were selected to cover six haplotypic blocks and were genotyped in 964 postmenopausal Spanish women. Haplotypes were established with HaploStats. Association was analysed by GLM (for BMD) and logistic regression (for fractures) both at single SNP and haplotype levels.

Results

Upon adjustment for multiple testing (p < 0.0073), one of the SNPs (SNP #17, rs1032129) remained significantly associated with FN BMD (p = 0.001). Four block-haplotypes stood multiple-testing correction. Two remained associated with FN BMD and two with fracture. The association of block-4 haplotype “AC” (of SNPs #18 and #17) with FN BMD (p = 0.0002) was stronger than that of SNP#17 alone and was the best result overall. A global assessment of the results indicated that all the alleles and haplotypes with a protective effect, at p < 0.05, belonged to a frequent long-range haplotype.

Conclusions

In conclusion, these results provide a detailed picture of the involvement of common variants and haplotypes of the OPG gene in bone phenotypes.

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Acknowledgments

The authors thank Isabel Aymar for technical assistance, Roberto Elosua (URLEC, IMIM) for help with the statistical analysis, and Robin Rycroft for revising the English. L.A. received a fellowship from the Generalitat de Catalunya. The CIBER de Enfermedades Raras (CIBERER) and the Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad (RETICEF) are initiatives of the ISCIII.

Conflicts of interest

None.

Funding sources

Grants FIS PI 060895 (Carlos III Health Institute, Science and Innovation Ministery); SAF2004-06085 and SAF2007-64654 (Spanish Ministry of Education and Science); GENOMOS Project: grant QLRT-2001-02629 (European Commission); Grant 2005SGR 00762 and 2005SGR 00848 (Catalan Department of Universities, Research and the Information Society).

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Authors and Affiliations

  1. Internal Medicine, URFOA, IMIM, RETICEF, Hospital del Mar, Autonomous University of Barcelona, Barcelona, Spain

    S. Jurado, X. Nogués, N. Garcia-Giralt, G. Yoskovitz, L. Mellibovsky & A. Díez-Pérez

  2. Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain

    L. Agueda, R. Urreizti, S. Balcells & D. Grinberg

  3. Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain

    L. Agueda, R. Urreizti, S. Balcells & D. Grinberg

  4. CIBER de Enfermedades Raras (CIBERER), Barcelona, Spain

    L. Agueda, R. Urreizti, S. Balcells & D. Grinberg

  5. Department of Rheumatology, URFOA, IMIM, RETICEF, Hospital del Mar, Autonomous University of Barcelona, Barcelona, Spain

    L. Pérez-Edo

  6. Department of Traumatology and Orthopaedic Surgery, URFOA, IMIM, RETICEF, Hospital del Mar, Autonomous University of Barcelona, Barcelona, Spain

    G. Saló

  7. Department of Gynecology and Obstetrics, URFOA, IMIM, RETICEF, Hospital del Mar, Autonomous University of Barcelona, Barcelona, Spain

    R. Carreras

  8. Institut Municipal d’Investigació Mèdica (IMIM), Parc de Rercerca Biomèdica (PRBB), Dr Aiguader 88, 08003, Barcelona, Spain

    S. Jurado

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  1. S. Jurado
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Correspondence to S. Jurado.

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Jurado, S., Nogués, X., Agueda, L. et al. Polymorphisms and haplotypes across the osteoprotegerin gene associated with bone mineral density and osteoporotic fractures. Osteoporos Int 21, 287–296 (2010). https://doi.org/10.1007/s00198-009-0956-4

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  • DOI: https://doi.org/10.1007/s00198-009-0956-4

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