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Title of Journal: Mol Cell Biochem

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Abbravation: Molecular and Cellular Biochemistry

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Springer US

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DOI

10.1002/ncr.4100590303

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1573-4919

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Exon array analysis reveals genetic heterogeneity

Authors: Isabel PérezNúñez José L PérezCastrillón María T Zarrabeitia Carmen GarcíaIbarbia Laura MartínezCalvo José M Olmos Laisa S Briongos Javier Riancho Victoria Camarero Josep M Muñoz Vives Raquel Cruz José A Riancho
Publish Date: 2015/07/10
Volume: 409, Issue: 1-2, Pages: 45-50
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Abstract

Atraumatic subtrochanteric and diaphyseal atypical femoral fractures are a rare but important adverse event in patients treated with potent antiresortive 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 genomewide analysis of up to 300000 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 25 × 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 = 26 × 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 genesIsabel PérezNúñez José L PérezCastrillón María T Zarrabeitia Carmen GarcíaIbarbia Laura MartínezCalvo 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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