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

Laura De-Ugarte, Enrique Caro-Molina, Maria Rodríguez-Sanz, Miguel Angel Garciá-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-Maciás, Javier Del Pino-Montes, Manuel Munõz-Torres, Manuel DIaz-Curiel, Jorge Malouf, Antonio Cano, José Luis Pérez-Castrillon, Xavier Nogues, Natalia Garcia-GiraltAdolfo DIez-Perez

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13 Citations (Scopus)


© 2017 The Author(s). 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.
Original languageEnglish
Article number516
Issue number1
Publication statusPublished - 1 Dec 2017


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