Genetic polymorphism of miR-196a-2 is associated with bone mineral density (BMD)

Karabegović, I. and Maas, S. and Medina-Gomez, C. and Zrimšek, M. and Reppe, S. and Gautvik, K. M. and Uitterlinden, A. G. and Rivadeneira, F. and Ghanbari, M. (2017) Genetic polymorphism of miR-196a-2 is associated with bone mineral density (BMD). International Journal of Molecular Sciences, 18 (12).

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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. © 2017 by the authors. Licensee MDPI, Basel, Switzerland.

Item Type: Article
Additional Information: Cited By :4 Export Date: 16 February 2020 Correspondence Address: Ghanbari, M.; Department of Epidemiology, Erasmus University Medical Center, ’s-Gravendijkwal 230, Netherlands; email: m.ghanbari@erasmusmc.nl
Uncontrolled Keywords: Bone mineral density Genetic variation GWAS MiRNA polymorphism Osteoporosis microRNA microRNA 196a 2 unclassified drug MIRN196 microRNA, human adult aged Article bone density female femoral neck forearm gender gene gene expression genetic association genetic variability genome-wide association study human lumbar spine major clinical study male microRNA 196a 2 gene phenotype RNA structure single nucleotide polymorphism genetics lumbar vertebra metabolism pathology Femur Neck Humans Lumbar Vertebrae MicroRNAs Polymorphism, Single Nucleotide
Subjects: WE Musculoskeletal system
QT physiology
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib3 lib3
Date Deposited: 27 Apr 2020 07:13
Last Modified: 27 Apr 2020 07:13
URI: http://eprints.mums.ac.ir/id/eprint/16883

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