caa a22 4500 606234675 CHVBK 20210128101238.0 cr unu---uuuuu 210128e20151101xx s 000 0 eng 10.1007/s11010-015-2510-3 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2510-3 Exon array analysis reveals genetic heterogeneity in atypical femoral fractures. A pilot study [Elektronische Daten] [Isabel Pérez-Núñez, José Pérez-Castrillón, María Zarrabeitia, Carmen García-Ibarbia, Laura Martínez-Calvo, José Olmos, Laisa Briongos, Javier Riancho, Victoria Camarero, Josep Muñoz Vives, Raquel Cruz, José Riancho] 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. Springer Science+Business Media New York, 2015 Atypical fractures nationallicence Polymorphisms nationallicence Genetic association study nationallicence Osteoporosis nationallicence Hedgehog nationallicence Rare variants nationallicence Pérez-Núñez Isabel Service of Traumatology and Orthopedic Surgery, Hospital U.M. Valdecilla, University of Cantabria, Santander, Spain aut Pérez-Castrillón José Service of Internal Medicine, Hospital U. Río Hortega, University of Valladolid, RETICEF, Valladolid, Spain aut Zarrabeitia María Unit of Legal Medicine, IDIVAL, University of Cantabria, Santander, Spain aut García-Ibarbia Carmen Service of Internal Medicine, Hospital U.M. Valdecilla, IDIVAL, University of Cantabria, RETICEF, Av Valdecilla sn, 39008, Santander, Spain aut Martínez-Calvo Laura Group of Genomic Medicine, Hospital U. Santiago, University of Santiago, CIBERER, Santiago de Compostela, Spain aut Olmos José Service of Internal Medicine, Hospital U.M. Valdecilla, IDIVAL, University of Cantabria, RETICEF, Av Valdecilla sn, 39008, Santander, Spain aut Briongos Laisa Service of Internal Medicine, Hospital U. Río Hortega, University of Valladolid, RETICEF, Valladolid, Spain aut Riancho Javier Service of Internal Medicine, Hospital U.M. Valdecilla, IDIVAL, University of Cantabria, RETICEF, Av Valdecilla sn, 39008, Santander, Spain aut Camarero Victoria Service of Internal Medicine, Hospital U.M. Valdecilla, IDIVAL, University of Cantabria, RETICEF, Av Valdecilla sn, 39008, Santander, Spain aut Muñoz Vives Josep Orthopedic Department, Hospital Verge de Meritxell, Escaldes-Engordany, Andorra aut Cruz Raquel Group of Genomic Medicine, Hospital U. Santiago, University of Santiago, CIBERER, Santiago de Compostela, Spain aut Riancho José Service of Internal Medicine, Hospital U.M. Valdecilla, IDIVAL, University of Cantabria, RETICEF, Av Valdecilla sn, 39008, Santander, Spain aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 409/1-2(2015-11-01), 45-50 0300-8177 409:1-2<45 2015 409 11010 https://doi.org/10.1007/s11010-015-2510-3 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2510-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Pérez-Núñez Isabel Service of Traumatology and Orthopedic Surgery, Hospital U.M. Valdecilla, University of Cantabria, Santander, Spain aut NATIONALLICENCE 700 1- Pérez-Castrillón José Service of Internal Medicine, Hospital U. Río Hortega, University of Valladolid, RETICEF, Valladolid, Spain aut NATIONALLICENCE 700 1- Zarrabeitia María Unit of Legal Medicine, IDIVAL, University of Cantabria, Santander, Spain aut NATIONALLICENCE 700 1- García-Ibarbia Carmen Service of Internal Medicine, Hospital U.M. Valdecilla, IDIVAL, University of Cantabria, RETICEF, Av Valdecilla sn, 39008, Santander, Spain aut NATIONALLICENCE 700 1- Martínez-Calvo Laura Group of Genomic Medicine, Hospital U. Santiago, University of Santiago, CIBERER, Santiago de Compostela, Spain aut NATIONALLICENCE 700 1- Olmos José Service of Internal Medicine, Hospital U.M. Valdecilla, IDIVAL, University of Cantabria, RETICEF, Av Valdecilla sn, 39008, Santander, Spain aut NATIONALLICENCE 700 1- Briongos Laisa Service of Internal Medicine, Hospital U. Río Hortega, University of Valladolid, RETICEF, Valladolid, Spain aut NATIONALLICENCE 700 1- Riancho Javier Service of Internal Medicine, Hospital U.M. Valdecilla, IDIVAL, University of Cantabria, RETICEF, Av Valdecilla sn, 39008, Santander, Spain aut NATIONALLICENCE 700 1- Camarero Victoria Service of Internal Medicine, Hospital U.M. Valdecilla, IDIVAL, University of Cantabria, RETICEF, Av Valdecilla sn, 39008, Santander, Spain aut NATIONALLICENCE 700 1- Muñoz Vives Josep Orthopedic Department, Hospital Verge de Meritxell, Escaldes-Engordany, Andorra aut NATIONALLICENCE 700 1- Cruz Raquel Group of Genomic Medicine, Hospital U. Santiago, University of Santiago, CIBERER, Santiago de Compostela, Spain aut NATIONALLICENCE 700 1- Riancho José Service of Internal Medicine, Hospital U.M. Valdecilla, IDIVAL, University of Cantabria, RETICEF, Av Valdecilla sn, 39008, Santander, Spain aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 409/1-2(2015-11-01), 45-50 0300-8177 409:1-2<45 2015 409 11010