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

Ugarte Corbalán, Laura de, 1988-; Caro-Molina, Enrique; Rodríguez Sanz, Maria, 1984-; Nogués Solán, Xavier; Garcia Giralt, Natàlia; Díez Pérez, Adolfo

doi:http://dx.doi.org/10.1038/s41598-017-00641-7

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

Citation

De-Ugarte L, Caro-Molina E, Rodríguez-Sanz M, García-Pérez MA, Olmos JM, Sosa-Henríquez M. et al. SNPs in bone-related miRNAs are associated with the osteoporotic phenotype. Sci Rep. 2017 Mar 31;7(1):516. DOI: 10.1038/s41598-017-00641-7

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