doi:10.1038/s41598-017-00641-7engDe-Ugarte, L.Caro-Molina, E.Rodríguez-Sanz, M.Garciá-Pérez, M. A.Olmos, J. M.Sosa-Henríquez, M.Pérez-Cano, R.Gómez-Alonso, C.Del Rio, L.Mateo-Agudo, J.Blázquez-Cabrera, J. A.González-Maciás, J.Pino-Montes, J.Munõz-Torres, M.DIaz-Curiel, M.Malouf, J.Cano, A.Pérez-Castrillon, J. L.Nogues, X.Garcia-Giralt, N.DIez-Perez, A.SNPs in bone-related miRNAs are associated with the osteoporotic phenotypeART-2017-98475Biogenesis 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.2017http://zaguan.unizar.es/record/6150910.1038/s41598-017-00641-7http://zaguan.unizar.es/record/61509oai:zaguan.unizar.es:61509info:eu-repo/grantAgreement/ES/ISCIII/RD12-0043-0022info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI13-00116info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI12-02775info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI12-02582info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI10-01537info:eu-repo/grantAgreement/ES/ISCIII/CB16-10-00245Scientific reports 7 (2017), 516 [10 pp.]byhttp://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccess