Identification of a miRNA Based-Signature Associated with Acute Coronary Syndrome: Evidence from the FLORINF Study
Abstract
:1. Introduction
2. Experimental Section
2.1. Study Population
2.2. Total RNA Isolation and Quality Control
2.3. MiRNA Expression Profiling
2.4. MiRNA Validation Phase
2.5. Statistical Analysis
3. Results
3.1. Screening of MiRNAs in the Derivation Cohort and Validation of Candidate miRNAs
3.2. Multivariate Analysis and Improved Predictive Value of the Clinical Model by Addition of the Selected miRNAs
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ACS | Acute coronary syndrome |
AMI | Acute myocardial infarction |
AUC | Area under the curve |
CAD | Coronary artery disease |
CVR | Cardiovascular risk |
MiRNA | Micro RNA |
RT-qPCR | Reverse transcription-quantitative polymerase chain reaction |
ROC | Receiver operating characteristic |
SCORE | Systematic Coronary Risk Evaluation |
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ACS (n = 80) | Controls (n = 80) | p Value | ||
---|---|---|---|---|
Gender (%) | Male | 82 | 58 | 0.001 |
Female | 18 | 42 | ||
Age (years) | 56.9 ± 9.4 | 60.1 ± 7.9 | 0.023 | |
Obesity (%) | 16 | 32 | 0.008 | |
Dyslipideamia (%) | 58 | 77 | 0.002 | |
Diabetes (%) | 19 | 24 | 0.86 | |
Hypertension (%) | 42 | 85 | <0.0001 | |
Current smoker (%) | 40 | 15 | <0.0001 | |
Heredity (%) | 29 | 34 | 0.76 | |
Blood glucose (mmol/L) | 116.8 ± 41.4 | 111.7 ± 58.4 | 0.03 | |
Triglycerides (mg/dL) | 146.1 ± 86.4 | 137.1 ± 70.6 | 0.59 | |
Total cholesterol (mg/dL) | 196.8 ± 44.5 | 199.2 ± 44.5 | 0.458 | |
LDL-cholesterol (mg/dL) a | 120.1 ± 38.1 | 119.3 ± 40.3 | 0.96 | |
HDL-cholesterol (mg/dL) b | 47.7 ± 11.7 | 52.8 ± 15.6 | 0.048 | |
Medical treatment at admsission | ||||
Beta blocker agents (%) | 17 | 27 | 0.12 | |
ACE inhibitors (%) c | 16 | 25 | 0.11 | |
Antiplatelet agents (%) | 17 | 26 | 0.16 | |
Statins (%) | 25 | 48 | 0.001 | |
ARA II (%) d | 10 | 41 | <0.0001 | |
Antidiabetic treatment (%) | 10 | 20 | 0.07 |
ACS (n = 80) Mean −ΔCt | SD | Controls (n = 80) Mean −ΔCt | SD | Fold Change | p Value | |
---|---|---|---|---|---|---|
let 7c | −6.834 | 1.299 | −7.06 | 1.247 | 1.270 | 0.2598 |
let 7g | −4.94 | 1.336 | −4.935 | 1.448 | 0.926 | 0.8921 |
miR-122 | −5.718 | 2.747 | −6.9 | 2.261 | 2.258 | 0.0011 |
miR-126 | −1.261 | 1.692 | −1.521 | 1.401 | 1.010 | 0.395 |
miR-133a | −7.481 | 2.398 | −7.551 | 2.07 | 1.010 | 0.5427 |
miR-139-5p | −6.822 | 1.525 | −7.147 | 1.295 | 0.962 | 0.2484 |
miR-145 | −4.728 | 1.552 | −4.536 | 1.74 | 0.861 | 0.4899 |
miR-146a | −2.238 | 1.733 | −2.523 | 1.637 | 1.057 | 0.3253 |
miR-146b | −4.513 | 1.54 | −4.58 | 1.5 | 1.000 | 0.828 |
miR-150 | −2.494 | 1.46 | −3.311 | 0.847 | 1.575 | 0.001 * |
miR-155 | −7.001 | 1.536 | −7.204 | 1.39 | 0.877 | 0.5137 |
miR-16 | 1.948 | 2.023 | 1.393 | 1.448 | 1.858 | 0.0017 * |
miR-186 | −5.35 | 1.879 | −5.815 | 1.661 | 1.238 | 0.0408 |
miR-195 | −4.187 | 1.839 | −4.572 | 1.348 | 1.723 | 0.0143 * |
miR-21 | −3.686 | 1.356 | −3.738 | 1.393 | 1.073 | 0.7035 |
miR-223-5p | −9.845 | 2.331 | −10.34 | 1.864 | 1.510 | 0.0429 |
miR-223-3p | −0.516 | 2.182 | −1.054 | 1.805 | 1.431 | 0.0825 |
miR-30b | −1.898 | 1.401 | −1.762 | 1.386 | 0.831 | 0.5495 |
miR-30c | −3.239 | 1.626 | −3.341 | 1.48 | 0.971 | 0.7111 |
miR-574-3p | −4.622 | 1.768 | −5.1 | 1.346 | 1.283 | 0.0582 * |
miR-92a | −1.009 | 1.554 | −1.59 | 1.229 | 1.551 | 0.0022 * |
Unadjusted | Adjusted | |||||
---|---|---|---|---|---|---|
OR | 95%CI | p Value | OR | 95%CI | p Value | |
miR-122 | ||||||
t2 vs. t1 | 0.68 | 0.31–1.50 | 0.34 | 0.79 | 0.26–2.37 | 0.67 |
t3 vs. t1 | 2.89 | 1.29–6.46 | 0.0096 | 3.94 | 1.28–12.1 | 0.017 |
Tertiles −7.0 and −5.15 | ||||||
miR-150 | ||||||
t2 vs. t1 | 1.23 | 0.56–2.70 | 0.61 | 1.17 | 0.38–3.64 | 0.79 |
t3 vs. t1 | 4.84 | 2.11–11.1 | 0.001 | 4.39 | 1.40–13.8 | 0.011 |
Tertiles −3.57 and −2.69 | ||||||
miR-16 | ||||||
t2 vs. t1 | 0.58 | 0.26–1.28 | 0.17 | 0.70 | 0.22–2.18 | 0.54 |
t3 vs. t1 | 3.48 | 1.53–7.91 | 0.0029 | 3.59 | 1.16–11.1 | 0.027 |
Tertiles 1.29 and 2.67 | ||||||
miR-195 | ||||||
t2 vs. t1 | 0.61 | 0.28–1.34 | 0.22 | 1.01 | 0.33–3.04 | 0.99 |
t3 vs. t1 | 3.39 | 1.49–7.72 | 0.0036 | 5.22 | 1.52–17.9 | 0.009 |
Tertiles −4.86 and −3.54 | ||||||
miR-92a | ||||||
t2 vs. t1 | 1.15 | 0.53–2.52 | 0.73 | 1.72 | 0.53–5.61 | 0.37 |
t3 vs. t1 | 3.08 | 1.39–6.85 | 0.0057 | 3.31 | 1.07–10.2 | 0.038 |
Tertiles −1.73 and −0.62 | ||||||
miR-186 | ||||||
t2 vs. t1 | 0.64 | 0.30–1.41 | 0.27 | 0.61 | 0.20–1.86 | 0.39 |
t3 vs. t1 | 2.37 | 1.08–5.22 | 0.032 | 2.47 | 0.85–7.17 | 0.09 |
Tertiles −6.11 and −4.83 | ||||||
miR-223-5p | ||||||
t2 vs. t1 | 1.08 | 0.50–2.32 | 0.85 | 0.94 | 0.31–2.84 | 0.92 |
t3 vs. t1 | 1.4 | 0.65–3.00 | 0.39 | 1.63 | 0.57–4.66 | 0.37 |
Tertiles −1.57 and 0 |
AUC | 95% CI | p Value | |
---|---|---|---|
Clinical model | 0.882 | (0.830–0.933) | - |
+ miR-122 | 0.903 | (0.856–0.950) | 0.13 |
+ miR-150 | 0.907 | (0.861–0.953) | 0.10 |
+ miR-195 | 0.887 | (0.842–0.946) | 0.30 |
+ miR-92a | 0.900 | (0.853–0.951) | 0.13 |
+ miR-16 | 0.896 | (0.845–0.946) | 0.27 |
+ miR-122+miR-150 | 0.911 | (0.866–0.956) | 0.07 |
+ miR-122+miR-195 | 0.915 | (0.873–0.956) | 0.07 |
+ miR-122+miR92a | 0.904 | (0.857–0.951) | 0.15 |
+ miR-122+miR16 | 0.909 | (0.684–0.954) | 0.09 |
+ miR-150+miR92a | 0.906 | (0.859–0.953) | 0.11 |
+ miR-150+miR-195 | 0.909 | (0.866–0.951) | 0.11 |
+ miR-150+miR16 | 0.909 | (0.866–0.953) | 0.07 |
+ miR-195+miR-92a | 0.906 | (0.862–0.951) | 0.15 |
+ miR-195+miR-16 | 0.908 | (0.865–0.951) | 0.10 |
+ miR-16+miR-92a | 0.901 | (0.855–0.947) | 0.30 |
+ miR-122+miR-150+miR-92a | 0.913 | (0.869–0.958) | 0.06 |
+ miR-122+miR-150+miR-195 | 0.925 | (0.886–0.964) | 0.02 |
+ miR-122+miR-150+miR-16 | 0.915 | (0.871–0.958) | 0.06 |
+ miR-150+miR-92a+miR-195 | 0.914 | (0.872–0.956) | 0.07 |
+ miR-150+miR-92a+miR-16 | 0.911 | (0.867–0.955) | 0.08 |
+ miR-16+miR-195+miR-92a | 0.909 | (0.865–0.952) | 0.15 |
+ miR-122+miR-195+miR-92a+miR-16 | 0.919 | (0.877–0.960) | 0.06 |
+ miR-122+miR-150+miR-195+miR-92a | 0.927 | (0.889–0.966) | 0.01 |
+ miR-122+miR-150+miR-195+miR-16 | 0.924 | (0.885–0.933) | 0.003 |
+ miR-150+miR-195+miR-92a+miR-16 | 0.917 | (0.876–0.958) | 0.07 |
+miR-122+miR-150+-miR-195+miR-92a+miR- 16 | 0.928 | (0.890–0.966) | 0.02 |
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Elbaz, M.; Faccini, J.; Laperche, C.; Grousset, E.; Roncalli, J.; Ruidavets, J.-B.; Vindis, C. Identification of a miRNA Based-Signature Associated with Acute Coronary Syndrome: Evidence from the FLORINF Study. J. Clin. Med. 2020, 9, 1674. https://doi.org/10.3390/jcm9061674
Elbaz M, Faccini J, Laperche C, Grousset E, Roncalli J, Ruidavets J-B, Vindis C. Identification of a miRNA Based-Signature Associated with Acute Coronary Syndrome: Evidence from the FLORINF Study. Journal of Clinical Medicine. 2020; 9(6):1674. https://doi.org/10.3390/jcm9061674
Chicago/Turabian StyleElbaz, Meyer, Julien Faccini, Clémence Laperche, Elisa Grousset, Jérôme Roncalli, Jean-Bernard Ruidavets, and Cécile Vindis. 2020. "Identification of a miRNA Based-Signature Associated with Acute Coronary Syndrome: Evidence from the FLORINF Study" Journal of Clinical Medicine 9, no. 6: 1674. https://doi.org/10.3390/jcm9061674