Genetic Polymorphism of miR-196a-2 is Associated with Bone Mineral Density (BMD)
AbstractMicroRNAs (miRNAs) are small non-coding RNA molecules that post-transcriptionally regulate the translation of messenger RNAs. Given the crucial role of miRNAs in gene expression, genetic variants within miRNA-related sequences may affect miRNA function and contribute to disease risk. Osteoporosis is characterized by reduced bone mass, and bone mineral density (BMD) is a major diagnostic proxy to assess osteoporosis risk. Here, we aimed to identify miRNAs that are involved in BMD using data from recent genome-wide association studies (GWAS) on femoral neck, lumbar spine and forearm BMD. Of 242 miRNA-variants available in the GWAS data, we found rs11614913:C > T in the precursor miR-196a-2 to be significantly associated with femoral neck-BMD (p-value = 9.9 × 10−7, β = −0.038) and lumbar spine-BMD (p-value = 3.2 × 10−11, β = −0.061). Furthermore, our sensitivity analyses using the Rotterdam study data showed a sex-specific association of rs11614913 with BMD only in women. Subsequently, we highlighted a number of miR-196a-2 target genes, expressed in bone and associated with BMD, that may mediate the miRNA function in BMD. Collectively, our results suggest that miR-196a-2 may contribute to variations in BMD level. Further biological investigations will give more insights into the mechanisms by which miR-196a-2 control expression of BMD-related genes. View Full-Text
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Karabegović, I.; Maas, S.; Medina-Gomez, C.; Zrimšek, M.; Reppe, S.; Gautvik, K.M.; Uitterlinden, A.G.; Rivadeneira, F.; Ghanbari, M. Genetic Polymorphism of miR-196a-2 is Associated with Bone Mineral Density (BMD). Int. J. Mol. Sci. 2017, 18, 2529.
Karabegović I, Maas S, Medina-Gomez C, Zrimšek M, Reppe S, Gautvik KM, Uitterlinden AG, Rivadeneira F, Ghanbari M. Genetic Polymorphism of miR-196a-2 is Associated with Bone Mineral Density (BMD). International Journal of Molecular Sciences. 2017; 18(12):2529.Chicago/Turabian Style
Karabegović, Irma; Maas, Silvana; Medina-Gomez, Carolina; Zrimšek, Maša; Reppe, Sjur; Gautvik, Kaare M.; Uitterlinden, André G.; Rivadeneira, Fernando; Ghanbari, Mohsen. 2017. "Genetic Polymorphism of miR-196a-2 is Associated with Bone Mineral Density (BMD)." Int. J. Mol. Sci. 18, no. 12: 2529.
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