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Exon array analysis reveals genetic heterogeneity in atypical femoral fractures. A pilot study

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Abstract

Atraumatic subtrochanteric and diaphyseal (atypical) femoral fractures are a rare, but important adverse event in patients treated with potent anti-resortive agents. The mechanisms involved are unknown and particularly the association with genetic variants has not been explored. The aim of the study was to identify rare genetic variants that could be associated with the occurrence of these fractures. We performed a genome-wide analysis of up to 300,000 variants, mainly distributed in gene coding regions, in 13 patients with atypical femoral fractures and 268 control women, either healthy or with osteoporosis. Twenty one loci were more frequent in the fracture group, with a nominal p value between 1 × 10−6 and 2.5 × 10−3. Most patients accumulated two or more allelic variants, and consequently the number of risk variants was markedly different between patients and controls (p = 2.6 × 10−22). The results of this pilot study suggest that these fractures are polygenic and are associated with the accumulation of changes in the coding regions of several genes.

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Acknowledgments

We acknowledge the technical assistance of Carolina Sañudo and Jana Arozamena.

Funding

Supported in part by grants from Instituto de Salud Carlos III that included FEDER funds from the EU (PI 12/0615 and PI 11/1092).

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Authors and Affiliations

  1. Service of Traumatology and Orthopedic Surgery, Hospital U.M. Valdecilla, University of Cantabria, Santander, Spain

    Isabel Pérez-Núñez

  2. Service of Internal Medicine, Hospital U. Río Hortega, University of Valladolid, RETICEF, Valladolid, Spain

    José L. Pérez-Castrillón & Laisa S. Briongos

  3. Unit of Legal Medicine, IDIVAL, University of Cantabria, Santander, Spain

    María T. Zarrabeitia

  4. Service of Internal Medicine, Hospital U.M. Valdecilla, IDIVAL, University of Cantabria, RETICEF, Av Valdecilla sn, 39008, Santander, Spain

    Carmen García-Ibarbia, José M. Olmos, Javier Riancho, Victoria Camarero & José A. Riancho

  5. Group of Genomic Medicine, Hospital U. Santiago, University of Santiago, CIBERER, Santiago de Compostela, Spain

    Laura Martínez-Calvo & Raquel Cruz

  6. Orthopedic Department, Hospital Verge de Meritxell, Escaldes-Engordany, Andorra

    Josep M. Muñoz Vives

Authors
  1. Isabel Pérez-Núñez
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  2. José L. Pérez-Castrillón
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  3. María T. Zarrabeitia
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  8. Javier Riancho
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  12. José A. Riancho
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Corresponding author

Correspondence to José A. Riancho.

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Conflict of interest

Isabel Pérez-Núñez, José L. Pérez-Castrillón, María T. Zarrabeitia, Carmen García-Ibarbia, Laura Martínez-Calvo, José M. Olmos, Laisa S. Briongos, Javier Riancho, Victoria Camarero, Josep M. Muñoz Vives, Raquel Cruz and José A. Riancho declare that they have no conflicts of interest.

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Pérez-Núñez, I., Pérez-Castrillón, J.L., Zarrabeitia, M.T. et al. Exon array analysis reveals genetic heterogeneity in atypical femoral fractures. A pilot study. Mol Cell Biochem 409, 45–50 (2015). https://doi.org/10.1007/s11010-015-2510-3

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