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

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 Sa

SUBMITTER: Ugartondo N 

PROVIDER: S-EPMC8303772 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature