Genetic Polymorphism of miR-196a-2 is Associated with Bone Mineral Density (BMD)
Abstract
:1. Introduction
2. Results
2.1. A Variant in miR-196a-2 Associates with BMD
2.2. The Potential Impact of rs11614913 on the miR-196a-2 Structure and Function
2.3. Associaton of miR-196a-2 Target Genes with BMD
2.4. Sensitivity Analyses for rs11614913 in miR-196a-2 Using the Rotterdam Study Data
3. Discussion
4. Materials and Methods
4.1. Genome-Wide Association Studies on BMD Phenotypes
4.2. Identification of Genetic Variants in miRNA-Encoding Sequences
4.3. miRNA Target Genes Associated with BMD Phenotypes
4.4. The Variant Effect on the Pre-miRNA Structure
4.5. The Rotterdam Study Data
5. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
GWAS | Genome-wide association studies |
GEFOS | Genetic factors for osteoporosis |
BMD SNP | Bone mineral density Single nucleotide polymorphism |
FN-BMD | Femoral neck bone mineral density |
LS-BMD | Lumbar spine bone mineral density |
FA-BMD | Forearm bone mineral density |
miRNA | microRNA |
WHR | Waist to hip ratio |
RS | Rotterdam Study |
DXA | Dual X-ray Absorptiometry |
MFE | Minimum free energy |
LD | Linkage disequilibrium |
DHEA | Dehydroepiandrosterone |
DHEAS | Dehydroepiandrosterone sulfate |
IQR | Interquartile range |
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miRNA ID | Associated Phenotype | Associated Target Genes | p-Value in GWAS Data | Top SNP |
---|---|---|---|---|
miR-196a-3p | JAG1 | 1.8 × 10−5 | rs2235811 | |
MACROD2 | 2.0 × 10−6 | rs365824 | ||
SP1 | 4.2 × 10−5 | rs4759334 | ||
JAG1 | 4.7 × 10−9 | rs2235811 | ||
ATF7 | 6.3 × 10−5 | rs1078358 | ||
MACROD2 | 8.1 × 10−5 | rs6110288 | ||
miR-196a-5p | FRMD4B | 5.6 × 10−4 | rs1564757 | |
NEDD4L | 9.6 × 10−4 | rs533502 | ||
BIRC6 | 1.2 × 10−3 | rs6737916 | ||
COL24A1 | 2.6 × 10−3 | rs1359419 | ||
RSPO2 | 3.1 × 10−3 | rs446454 | ||
DIP2A | 3.3 × 10−3 | rs2330593 |
Variables | Men | Women | |
---|---|---|---|
FN-BMD (g/cm2) | 0.95 (0.14) | 0.87 (0.14) | |
LS-BMD (g/cm2) | 1.20 (0.19) | 1.08 (0.19) | |
Age (years) | 65.71 (10.45) | 66.29 (10.61) | |
Weight (kg) | 85.55 (12.85) | 73.11 (13.09) | |
WHR | 0.95 (0.07) | 0.84 (0.07) | |
Height (cm) | 176.41 (7.01) | 162.73 (6.50) | |
Alcohol (g/day) | 9.29 (3.57–20.00) | 4.29 (0.54–10.00) | |
DHEA (nmol/L) | 11.82 (7.32) | 12.31 (7.65) | |
DHEAS (nmol/L) | 3200.18 (1757.16) | 2099.17 (1337.77) | |
Androstenedione (nmol/L) | 3.24 (1.27) | 2.70 (1.29) | |
Testosterone (nmol/L) | 17.53 (5.78) | 0.90 (0.45) | |
Estradiol (pmol/L) | 96.93 (33.82) | 38.86 (33.18) | |
Smoking | never smoker | 1125 (42.9%) | 2071 (58.8%) |
former smoker | 1039 (39.7%) | 841 (23.9%) | |
current smoker | 456 (17.4%) | 612 (17.4%) | |
Bone drugs | no | 2607 (99.5%) | 3400 (96.5%) |
yes | 13 (0.5%) | 124 (3.5%) |
Phenotype | Model | Men | Women | Combined | ||||||
---|---|---|---|---|---|---|---|---|---|---|
β | 95%CI | p-Value | β | 95%CI | p-v | β | 95%CI | p-Value | ||
FN-BMD | M1 | 0.004 | −0.003, 0.011 | 0.257 | 0.009 | 0.003, 0.014 | 0.003 | 0.007 | 0.003, 0.012 | 0.002 |
M2 | 0.004 | −0.003, 0.011 | 0.267 | 0.008 | 0.003, 0.014 | 0.003 | 0.007 | 0.003, 0.012 | 0.002 | |
M3 | 0.004 | −0.004, 0.011 | 0.319 | 0.008 | 0.003, 0.014 | 0.003 | 0.007 | 0.002, 0.011 | 0.003 | |
LS-BMD | M1 | 0.005 | −0.006, 0.016 | 0.380 | 0.010 | 0.001, 0.019 | 0.023 | 0.009 | 0.002, 0.016 | 0.011 |
M2 | 0.004 | −0.007, 0.015 | 0.423 | 0.010 | 0.001, 0.018 | 0.026 | 0.009 | 0.002, 0.016 | 0.012 | |
M3 | 0.003 | −0.008, 0.014 | 0.573 | 0.009 | 0.001, 0.018 | 0.038 | 0.008 | 0.001, 0.015 | 0.020 |
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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. https://doi.org/10.3390/ijms18122529
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. https://doi.org/10.3390/ijms18122529
Chicago/Turabian StyleKarabegović, Irma, Silvana Maas, Carolina Medina-Gomez, Maša Zrimšek, Sjur Reppe, Kaare M. Gautvik, André G. Uitterlinden, Fernando Rivadeneira, and Mohsen Ghanbari. 2017. "Genetic Polymorphism of miR-196a-2 is Associated with Bone Mineral Density (BMD)" International Journal of Molecular Sciences 18, no. 12: 2529. https://doi.org/10.3390/ijms18122529