http://www.cnr.it/ontology/cnr/individuo/prodotto/ID286876
A non-synonymous TNFRSF11A variation increases NFkB activity and the severity of Paget's disease (Articolo in rivista)
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- Label
- A non-synonymous TNFRSF11A variation increases NFkB activity and the severity of Paget's disease (Articolo in rivista) (literal)
- Anno
- 2011-01-01T00:00:00+01:00 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
- 10.1002/jbmr.542 (literal)
- Alternative label
Gianfrancesco F., Rendina D., Di Stefano M., Mingione A., Esposito T., Merlotti D., Gallone S., Magliocca S., Goode A., Formicola D., Morello G., Layfield R., Frattini A., De Filippo G., Nuti R., Searle M., Strazzullo P., Isaia G., Mossetti G., Gennari L. (2011)
A non-synonymous TNFRSF11A variation increases NFkB activity and the severity of Paget's disease
in Journal of bone and mineral research
(literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- Gianfrancesco F., Rendina D., Di Stefano M., Mingione A., Esposito T., Merlotti D., Gallone S., Magliocca S., Goode A., Formicola D., Morello G., Layfield R., Frattini A., De Filippo G., Nuti R., Searle M., Strazzullo P., Isaia G., Mossetti G., Gennari L. (literal)
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- Gianfrancesco F. Institute of Genetics and Biophysics ''Adriano Buzzati-Traverso, CNR Naples, Italy
Rendina D. Department of Clinical and Experimental Medicine, Federico II University Medical School, Naples, Italy
Di Stefano M. Department of Internal Medicine, University of Turin, Turin, Italy
Mingione A. Institute of Genetics and Biophysics ''Adriano Buzzati-Traverso, CNR Naples, Italy
Esposito T. Institute of Genetics and Biophysics ''Adriano Buzzati-Traverso, CNR Naples, Italy
Merlotti D. Department of Internal Medicine, Endocrine-Metabolic Sciences and Biochemistry, University of Siena, Siena, Italy
Gallone S. Department of Neuroscience, University of Turin, Turin, Italy
Magliocca S. Institute of Genetics and Biophysics ''Adriano Buzzati-Traverso, CNR Naples, Italy
Goode A. School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, United Kingdom
Formicola D. Institute of Genetics and Biophysics ''Adriano Buzzati-Traverso, CNR Naples, Italy
Morello G. Institute of Genetics and Biophysics ''Adriano Buzzati-Traverso, CNR Naples, Italy
Layfield R. School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, United Kingdom
Frattini A., Institute of Biomedical Technologies, National Research Council of Italy, Segrate, Milan, Italy
De Filippo G. Department of Clinical and Experimental Medicine, Federico II University Medical School, Naples, Italy
Nuti R., Department of Internal Medicine, Endocrine-Metabolic Sciences and Biochemistry, University of Siena, Siena, Italy
Searle M. Centre for Biomolecular Sciences, School of Chemistry, University Park, Nottingham, United Kingdom
Strazzullo P. Department of Clinical and Experimental Medicine, Federico II University Medical School, Naples, Italy
Isaia G. Department of Internal Medicine, University of Turin, Turin, Italy
Mossetti G. Department of Clinical and Experimental Medicine, Federico II University Medical School, Naples, Italy
Gennari L. Department of Internal Medicine, Endocrine-Metabolic Sciences and Biochemistry, University of Siena, Siena, Italy (literal)
- Titolo
- A non-synonymous TNFRSF11A variation increases NFkB activity and the severity of Paget's disease (literal)
- Abstract
- Mutations in the SQSTM1 gene were identified as a common cause of Paget's disease of bone (PDB) but experimental evidence
demonstrated that SQSTM1 mutation is not sufficient to induce PDB in vivo. Here, we identified two nonsynonymous single nucleotide
polymorphisms (SNPs) (C421T, H141Y and T575C, V192A) in the TNFRSF11A gene, associated with PDB and with the severity of
phenotype in a large population of 654 unrelated patients that were previously screened for SQSTM1 gene mutations. The largest effect
was found for the T575C variant, yielding an odds ratio of 1.29 (p¼0.003), with the C allele as the risk allele. Moreover, an even more
significant p-value (p¼0.0002) was observed in the subgroup of patients with SQSTM1 mutation, with an odds ratio of 1.71. Interestingly,
patients with the C allele also showed an increased prevalence of polyostotic disease (68%, 53%, and 51% in patients with CC, CT, and TT
genotypes, respectively; p¼0.01), as well as an increased number of affected skeletal sites (2.9, 2.5, and 2.0 in patients with CC, CT, and TT
genotypes, respectively, p¼0.008). These differences increased when analyses were restricted to cases with SQSTM1 mutation. In human
cell lines, cotrasfection with mutated SQSTM1 and TNFRSF11AA192 produced a level of activation of NFkB signaling greater than
cotrasfection with wild-type SQSTM1 and TNFRSF11AV192, confirming genetics and clinical evidences. These results provide the first
evidence that genetic variation within the OPG/RANK/RANKL system influences the severity of PBD in synergistic action with SQSTM1
gene mutations (literal)
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