Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.1/10678
Título: Effect of genetic variants of OPTN in the pathophysiology of Paget's disease of bone
Autor: Silva, Iris A. L.
Conceição, Natércia
Gagnon, Édith
Caiado, Helena
Brown, Jacques P.
Gianfrancesco, Fernando
Michou, Laëtitia
Cancela, Leonor
Palavras-chave: Case-control studies
Cells cultured
Female
Genetic Association Studies
Genetic predisposition to disease
HEK293 Cells
Humans
Male
Osteitis deformans
Promoter regions genetic
Transcription Factor TFIIIA
Polymorphism single nucleotide
Data: 2018
Editora: Elsevier
Resumo: Paget's disease of bone (PDB) is the second most frequent metabolic bone disease after osteoporosis. Genetic factors play an important role in PDB, but to date PDB causing mutations were identified only in the Sequestosome 1 gene at the PDB3 locus. OPTN has been recently associated with PDB, however little is known about the effect of genetic variants in this gene in PDB pathophysiology. By sequencing OPTN in SQSTM1 non-carriers PDB patients we found 16 SNPs in regulatory, coding and non-coding regions. One of those was found to be associated with PDB in our cohort - rs2234968. Our results show that rs2238968 effect may be explained by a change in OPTN splicing that give rise to a predicted truncated protein. We also performed functional studies on the variants located in OPTN promoter - rs3829923 and the rare variant -9906 - to investigate putative regulators of OPTN. Our results show that OPTN expression seems to be regulated by SP1, RXR, E47, and the E2F family. In conclusion, our work suggests a potential pathophysiological role of SNPs in OPTN, giving a new perspective about the regulatory mechanisms of this gene. Ultimately we discovered a new variant associated with PDB in OPTN, reinforcing the relevance of this gene for the development of this bone disease.
Peer review: yes
URI: http://hdl.handle.net/10400.1/10678
DOI: 10.1016/j.bbadis.2017.10.008
ISSN: 0925-4439
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