Gene Network of Susceptibility to Atypical Femoral Fractures Related to Bisphosphonate Treatment

Atypical femoral fractures (AFF) are rare fragility fractures in the subtrocantheric or diaphysis femoral region associated with long-term bisphosphonate (BP) treatment. The etiology of AFF is still unclear even though a genetic basis is suggested. We performed whole exome sequencing (WES) analysis...

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Detalles Bibliográficos
Autores: Garcia Giralt, Natàlia, Roca Ayats, Neus, Abril Ferrando, Josep Francesc, 1970-, Martínez-Gil, Núria, Ovejero, Diana, Castañeda, Santos, Nogués Solán, Xavier, Grinberg Vaisman, Daniel Raúl, Balcells Comas, Susana, Rabionet Janssen, Raquel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/183981
Acceso en línea:https://hdl.handle.net/2445/183981
Access Level:acceso abierto
Palabra clave:Fractures
Fèmur
Femur
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spelling Gene Network of Susceptibility to Atypical Femoral Fractures Related to Bisphosphonate TreatmentGarcia Giralt, NatàliaRoca Ayats, NeusAbril Ferrando, Josep Francesc, 1970-Martínez-Gil, NúriaOvejero, DianaCastañeda, SantosNogués Solán, XavierGrinberg Vaisman, Daniel RaúlBalcells Comas, SusanaRabionet Janssen, RaquelFracturesFèmurFracturesFemurAtypical femoral fractures (AFF) are rare fragility fractures in the subtrocantheric or diaphysis femoral region associated with long-term bisphosphonate (BP) treatment. The etiology of AFF is still unclear even though a genetic basis is suggested. We performed whole exome sequencing (WES) analysis of 12 patients receiving BPs for at least 5 years who sustained AFFs and 4 controls, also long-term treated with BPs but without any fracture. After filtration and prioritization of rare variants predicted to be damaging and present in genes shared among at least two patients, a total of 272 variants in 132 genes were identified. Twelve of these genes were known to be involved in bone metabolism and/or AFF, highlighting DAAM2 and LRP5, both involved in the Wnt pathway, as the most representative. Afterwards, we intersected all mutated genes with a list of 34 genes obtained from a previous study of three sisters with BP-related AFF, identifying nine genes. One of these (MEX3D) harbored damaging variants in two AFF patients from the present study and one shared among the three sisters. Gene interaction analysis using the AFFNET web suggested a complex network among bone-related genes as well as with other mutated genes. BinGO biological function analysis highlighted cytoskeleton and cilium organization. In conclusion, several genes and their interactions could provide genetic susceptibility to AFF, that along with BPs treatment and in some cases with glucocorticoids may trigger this so feared complication.MDPI2022202220222022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion11 p.application/pdfhttps://hdl.handle.net/2445/183981Articles publicats en revistes (Genètica, Microbiologia i Estadística)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.3390/genes13010146Genes, 2022, vol. 13, num. 1, p. 1-11https://doi.org/10.3390/genes13010146cc-by (c) Garcia Giralt, Natàlia et al., 2022https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1839812026-05-29T05:05:01Z
dc.title.none.fl_str_mv Gene Network of Susceptibility to Atypical Femoral Fractures Related to Bisphosphonate Treatment
title Gene Network of Susceptibility to Atypical Femoral Fractures Related to Bisphosphonate Treatment
spellingShingle Gene Network of Susceptibility to Atypical Femoral Fractures Related to Bisphosphonate Treatment
Garcia Giralt, Natàlia
Fractures
Fèmur
Fractures
Femur
title_short Gene Network of Susceptibility to Atypical Femoral Fractures Related to Bisphosphonate Treatment
title_full Gene Network of Susceptibility to Atypical Femoral Fractures Related to Bisphosphonate Treatment
title_fullStr Gene Network of Susceptibility to Atypical Femoral Fractures Related to Bisphosphonate Treatment
title_full_unstemmed Gene Network of Susceptibility to Atypical Femoral Fractures Related to Bisphosphonate Treatment
title_sort Gene Network of Susceptibility to Atypical Femoral Fractures Related to Bisphosphonate Treatment
dc.creator.none.fl_str_mv Garcia Giralt, Natàlia
Roca Ayats, Neus
Abril Ferrando, Josep Francesc, 1970-
Martínez-Gil, Núria
Ovejero, Diana
Castañeda, Santos
Nogués Solán, Xavier
Grinberg Vaisman, Daniel Raúl
Balcells Comas, Susana
Rabionet Janssen, Raquel
author Garcia Giralt, Natàlia
author_facet Garcia Giralt, Natàlia
Roca Ayats, Neus
Abril Ferrando, Josep Francesc, 1970-
Martínez-Gil, Núria
Ovejero, Diana
Castañeda, Santos
Nogués Solán, Xavier
Grinberg Vaisman, Daniel Raúl
Balcells Comas, Susana
Rabionet Janssen, Raquel
author_role author
author2 Roca Ayats, Neus
Abril Ferrando, Josep Francesc, 1970-
Martínez-Gil, Núria
Ovejero, Diana
Castañeda, Santos
Nogués Solán, Xavier
Grinberg Vaisman, Daniel Raúl
Balcells Comas, Susana
Rabionet Janssen, Raquel
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Fractures
Fèmur
Fractures
Femur
topic Fractures
Fèmur
Fractures
Femur
description Atypical femoral fractures (AFF) are rare fragility fractures in the subtrocantheric or diaphysis femoral region associated with long-term bisphosphonate (BP) treatment. The etiology of AFF is still unclear even though a genetic basis is suggested. We performed whole exome sequencing (WES) analysis of 12 patients receiving BPs for at least 5 years who sustained AFFs and 4 controls, also long-term treated with BPs but without any fracture. After filtration and prioritization of rare variants predicted to be damaging and present in genes shared among at least two patients, a total of 272 variants in 132 genes were identified. Twelve of these genes were known to be involved in bone metabolism and/or AFF, highlighting DAAM2 and LRP5, both involved in the Wnt pathway, as the most representative. Afterwards, we intersected all mutated genes with a list of 34 genes obtained from a previous study of three sisters with BP-related AFF, identifying nine genes. One of these (MEX3D) harbored damaging variants in two AFF patients from the present study and one shared among the three sisters. Gene interaction analysis using the AFFNET web suggested a complex network among bone-related genes as well as with other mutated genes. BinGO biological function analysis highlighted cytoskeleton and cilium organization. In conclusion, several genes and their interactions could provide genetic susceptibility to AFF, that along with BPs treatment and in some cases with glucocorticoids may trigger this so feared complication.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/183981
url https://hdl.handle.net/2445/183981
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/genes13010146
Genes, 2022, vol. 13, num. 1, p. 1-11
https://doi.org/10.3390/genes13010146
dc.rights.none.fl_str_mv cc-by (c) Garcia Giralt, Natàlia et al., 2022
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Garcia Giralt, Natàlia et al., 2022
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 11 p.
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Articles publicats en revistes (Genètica, Microbiologia i Estadística)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.81155

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