Next Article in Journal
IL-37 Targets TSLP-Primed Basophils to Alleviate Atopic Dermatitis
Next Article in Special Issue
Site-Specific Fracture Healing: Comparison between Diaphysis and Metaphysis in the Mouse Long Bone
Previous Article in Journal
Calcium and Heart Failure: How Did We Get Here and Where Are We Going?
Article

Functional Analyses of Four CYP1A1 Missense Mutations Present in Patients with Atypical Femoral Fractures

1
Department of Genetics, Microbiology and Statistics, Faculty of Biology, Universitat de Barcelona, CIBERER, IBUB, IRSJD, 08028 Barcelona, Spain
2
Musculoskeletal Research Group, IMIM (Hospital del Mar Medical Research Institute), Centro de Investigación Biomédica en Red en Fragilidad y Envejecimiento Saludable (CIBERFES), ISCIII, 08003 Barcelona, Spain
*
Authors to whom correspondence should be addressed.
Academic Editor: José Manuel López
Int. J. Mol. Sci. 2021, 22(14), 7395; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147395
Received: 26 May 2021 / Revised: 2 July 2021 / Accepted: 5 July 2021 / Published: 9 July 2021
(This article belongs to the Special Issue Bone Development and Growth)
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. View Full-Text
Keywords: CYP1A1; osteoporosis; atypical femoral fractures; bisphosphonates CYP1A1; osteoporosis; atypical femoral fractures; bisphosphonates
Show Figures

Figure 1

MDPI and ACS Style

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, 22, 7395. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147395

AMA Style

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. International Journal of Molecular Sciences. 2021; 22(14):7395. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147395

Chicago/Turabian Style

Ugartondo, Nerea, Núria Martínez-Gil, Mònica Esteve, Natàlia Garcia-Giralt, Neus Roca-Ayats, Diana Ovejero, Xavier Nogués, Adolfo Díez-Pérez, Raquel Rabionet, Daniel Grinberg, and Susanna Balcells. 2021. "Functional Analyses of Four CYP1A1 Missense Mutations Present in Patients with Atypical Femoral Fractures" International Journal of Molecular Sciences 22, no. 14: 7395. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147395

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop