@article{10902/28204,
year = {2022},
url = {https://hdl.handle.net/10902/28204},
abstract = {Osteoporosis is a skeletal disorder defined by a decreased bone mineral density (BMD) and an increased susceptibility to fractures. Bisphosphonates and selective oestrogen receptor modulators (SERM) are among the most widely used drugs. They inhibit bone resorption by targeting the mevalonate and oestrogen pathways, respectively. The aim of this study was to determine if common variants of genes in those pathways influence drug responses. We studied 192 women treated with oral aminobisphosphonates and 51 with SERMs. Genotypes at 154 SNPs of the mevalonate pathway and 806 in the oestrogen pathway were analyzed. Several SNPs located in genes FDPS and FNTA were associated with the bisphosphonate-induced changes in hip bone mineral density (BMD), whereas polymorphisms of the PDSS1, CYP19A1, CYP1A1, and CYP1A2 genes were associated with SERM-induced changes in spine BMD. After multivariate analyses, genotypes combining genes FDPS and FNTA showed a stronger association with bisphosphonate response (r = 0.34; p = 0.00009), whereas the combination of CYP19A1 and PDSS1 genotypes was associated with the response to SERMs (r = 0.62, p = 0.0003). These results suggest that genotyping genes in these pathways may help predict the response to antiresorptive drugs and hence make personalized therapeutic choices.},
organization = {Funding: Supported by grants from Instituto de Salud Carlos III (PI18/00762; PI21/00532) that could be cofunded by European Union FEDER funds. Genotyping service was carried out at CEGEN-PRB3-ISCIII; it is supported by grant PT17/0019, of the PE I+D+i 2013–2016, funded by ISCIII and ERDF.
Acknowledgments: Alvaro del Real received support by the postdoctoral grant Augusto Gonzalez de Linares of the University of Cantabria. We thank the skilful technical assistance of Carolina Sañudo and Alicia Martin-Rebollo.},
publisher = {MDPI},
publisher = {Pharmaceutics 2022, 14, 776},
title = {Pharmacogenetics of osteoporosis: a pathway analysis of the genetic influence on the effects of antiresorptive drugs},
author = {Real Bolt, Álvaro del and Valero Díaz de Lamadrid, Carmen and Olmos Martínez, José Manuel and Hernández Hernández, José Luis and Riancho Moral, José Antonio},
}