Welcome to the UPF Digital Repository

Functional analyses of four CYP1A1 missense mutations present in patients with atypical femoral fractures

Show simple item record

dc.contributor.author Ugartondo, Nerea
dc.contributor.author Martínez-Gil, Núria
dc.contributor.author Esteve, Mònica
dc.contributor.author Garcia Giralt, Natàlia
dc.contributor.author Roca Ayats, Neus
dc.contributor.author Ovejero Crespo, Diana
dc.contributor.author Nogués Solan, Francesc Xavier
dc.contributor.author Díez Pérez, Adolfo
dc.contributor.author Rabionet, Raquel
dc.contributor.author Grinberg, Daniel
dc.contributor.author Balcells, Susana
dc.date.accessioned 2022-03-01T07:05:37Z
dc.date.available 2022-03-01T07:05:37Z
dc.date.issued 2021
dc.identifier.citation Ugartondo N, Martínez-Gil N, Esteve M, Garcia-Giralt N, Roca-Ayats N, Ovejero D, Nogués X, Díez-Pérez A, Rabionet R, Grinberg D, Balcells S. Functional analyses of four CYP1A1 missense mutations present in patients with atypical femoral fractures. Int J Mol Sci. 2021 Jul 9;22(14):7395. DOI: 10.3390/ijms22147395
dc.identifier.issn 1422-0067
dc.identifier.uri http://hdl.handle.net/10230/52592
dc.description.abstract Osteoporosis is the most common metabolic bone disorder and nitrogen-containing bisphosphonates (BP) are a first line treatment for it. Yet, atypical femoral fractures (AFF), a rare adverse effect, may appear after prolonged BP administration. Given the low incidence of AFF, an underlying genetic cause that increases the susceptibility to these fractures is suspected. Previous studies uncovered rare CYP1A1 mutations in osteoporosis patients who suffered AFF after long-term BP treatment. CYP1A1 is involved in drug metabolism and steroid catabolism, making it an interesting candidate. However, a functional validation for the AFF-associated CYP1A1 mutations was lacking. Here we tested the enzymatic activity of four such CYP1A1 variants, by transfecting them into Saos-2 cells. We also tested the effect of commonly used BPs on the enzymatic activity of the CYP1A1 forms. We demonstrated that the p.Arg98Trp and p.Arg136His CYP1A1 variants have a significant negative effect on enzymatic activity. Moreover, all the BP treatments decreased CYP1A1 activity, although no specific interaction with CYP1A1 variants was found. Our results provide functional support to the hypothesis that an additive effect between CYP1A1 heterozygous mutations p.Arg98Trp and p.Arg136His, other rare mutations and long-term BP exposure might generate susceptibility to AFF.
dc.description.sponsorship Funding was available from Fundación Española de Investigación Ósea y Metabolismo Mineral (“Beca FEIOMM 2019 de Investigación Básica”) and grant PID2019-107188RB-C21 from the Spanish Ministerio de Ciencia e Innovación. N.M.G. and N.R.A. were recipients of Ph.D. fellowships from AGAUR (Catalan Government) and the Spanish Ministerio de Universidades.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher MDPI
dc.relation.ispartof Int J Mol Sci. 2021 Jul 9;22(14):7395
dc.rights © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Functional analyses of four CYP1A1 missense mutations present in patients with atypical femoral fractures
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.3390/ijms22147395
dc.subject.keyword CYP1A1
dc.subject.keyword Atypical femoral fractures
dc.subject.keyword Bisphosphonates
dc.subject.keyword Osteoporosis
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-107188RB-C21
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


This item appears in the following Collection(s)

Show simple item record

Search DSpace

Advanced Search


My Account


Compliant to Partaking