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Int. J. Mol. Sci. 2017, 18(12), 2529; https://doi.org/10.3390/ijms18122529

Genetic Polymorphism of miR-196a-2 is Associated with Bone Mineral Density (BMD)

1
Department of Epidemiology, Erasmus University Medical Center, ’s-Gravendijkwal 230, 3015 CE Rotterdam, the Netherlands
2
Department of Internal Medicine, Erasmus University Medical Center, ’s-Gravendijkwal 230, 3015 CE Rotterdam, the Netherlands
3
Department of Medical Biochemistry, Oslo University Hospital, Ullevaal, 0450 Oslo, Norway
4
Unger-Vetlesen Institute, Oslo Diakonale Hospital, 0456 Oslo, Norway
5
Department of Molecular Medicine, University of Oslo, 0372 Oslo, Norway
6
Department of Genetics, School of Medicine, Mashhad University of Medical Sciences, 91388-13944 Mashhad, Iran
*
Author to whom correspondence should be addressed.
Received: 1 November 2017 / Revised: 22 November 2017 / Accepted: 23 November 2017 / Published: 25 November 2017
(This article belongs to the Collection Human Single Nucleotide Polymorphisms and Disease Diagnostics)
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Abstract

MicroRNAs (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
Keywords: miRNA polymorphism; bone mineral density; osteoporosis; genetic variation; GWAS miRNA polymorphism; bone mineral density; osteoporosis; genetic variation; GWAS
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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.

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