SNPs in bone-related miRNAs are associated with the osteoporotic phenotype

Abstract Biogenesis and function of microRNAs can be influenced by genetic variants in the pri-miRNA sequences leading to phenotypic variability. This study aims to identify single nucleotide polymorphisms (SNPs) affecting the expression levels of bone-related mature microRNAs and thus, triggering a...

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Autores principales: Laura De-Ugarte, Enrique Caro-Molina, Maria Rodríguez-Sanz, Miguel Angel García-Pérez, José M. Olmos, Manuel Sosa-Henríquez, Ramón Pérez-Cano, Carlos Gómez-Alonso, Luis Del Rio, Jesús Mateo-Agudo, José Antonio Blázquez-Cabrera, Jesús González-Macías, Javier del Pino-Montes, Manuel Muñoz-Torres, Manuel Diaz-Curiel, Jorge Malouf, Antonio Cano, José Luis Pérez-Castrillon, Xavier Nogues, Natalia Garcia-Giralt, Adolfo Diez-Perez
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/b02685a070da4fae9bc27bc45550d851
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Sumario:Abstract Biogenesis and function of microRNAs can be influenced by genetic variants in the pri-miRNA sequences leading to phenotypic variability. This study aims to identify single nucleotide polymorphisms (SNPs) affecting the expression levels of bone-related mature microRNAs and thus, triggering an osteoporotic phenotype. An association analysis of SNPs located in pri-miRNA sequences with bone mineral density (BMD) was performed in the OSTEOMED2 cohort (n = 2183). Functional studies were performed for assessing the role of BMD-associated miRNAs in bone cells. Two SNPs, rs6430498 in the miR-3679 and rs12512664 in the miR-4274, were significantly associated with femoral neck BMD. Further, we measured these BMD-associated microRNAs in trabecular bone from osteoporotic hip fractures comparing to non-osteoporotic bone by qPCR. Both microRNAs were found overexpressed in fractured bone. Increased matrix mineralization was observed after miR-3679-3p inhibition in human osteoblastic cells. Finally, genotypes of rs6430498 and rs12512664 were correlated with expression levels of miR-3679 and miR-4274, respectively, in osteoblasts. In both cases, the allele that generated higher microRNA expression levels was associated with lower BMD values. In conclusion, two osteoblast-expressed microRNAs, miR-3679 and miR-4274, were associated with BMD; their overexpression could contribute to the osteoporotic phenotype. These findings open new areas for the study of bone disorders.