Eosinophil microRNAs Play a Regulatory Role in Allergic Diseases Included in the Atopic March
Abstract
:1. Introduction
2. Results
2.1. Differential Counts of Pri-miRNA Associated with Allergic Diseases Included in the Atopic March
2.2. Clustering of Significant miRNAs
2.3. Identifiaction of Possible Gene Targets
3. Discussion
4. Materials and Methods
4.1. SLSJ Asthma Cohort
4.2. Isolation of RNA from Eosinophils and Sequencing
4.3. Statistical Methods
4.3.1. Analyses of Pri-miRNA Expression Counts between Individuals
4.3.2. Clustering of miRNAs
4.3.3. Identification of Possible Gene Targets for Associated Pri-miRNAs
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Eosinophil Samples a (n = 145) | Affected b (n = 130) | Unaffected c (n = 15) | |
---|---|---|---|
M:F ratio | 1:1.04 | 1:1.09 | 1:0.67 |
Age, mean (range) | 46 (18–81) | 45 (18–81) | 55 (22–72) |
Age, median | 47 | 60 | 44 |
Smoking status d | |||
Non-smokers, n (%) | 93 (64) | 88 (68) | 5 (33) |
Ex-smokers, n (%) | 29 (20) | 22 (17) | 7 (47) |
Smokers, n (%) | 22 (15) | 19 (15) | 3 (20) |
PC20, mean mg/mL (SD) e | 1.76 (1.67) | 1.5 (1.57) | 3.75 (0.76) |
IgE, mean µg/L (SD) f | 4.93 (1.67) | 5.09 (1.67) | 3.61 (0.97) |
FEV1, mean% pred. (range) g | 94.72 (31–146) | 94.25 (31–46) | 98.6 (65–119) |
FEV1/FVC ratio, mean (range) h | 79.09 (38–97) | 94.25 (38–97) | 82.43 (68–96) |
White blood cell count i | |||
Eosinophil, mean × 109/L (%) | 0.25 (3.76) | 0.26 (3.96) | 0.15 (2.18) |
Lymphocyte, mean × 109/L (%) | 2.15 (32.12) | 2.15 (32.05) | 2.03 (31.43) |
Monocyte, mean × 109/L (%) | 0.52 (7.89) | 0.53 (7.88) | 0.50 (8.01) |
Neutrophil, mean × 109/L (%) | 3.80 (55.60) | 3.82 (55.45) | 3.72 (57.89) |
Basophil, mean × 109/L (%) | 0.04 (0.78) | 0.05 (0.77) | 0.04 (0.89) |
Asthma, n (%) j | 89 (61.81) | ||
Allergic rhinitis, n (%) k | 54 (37.50) | ||
Atopic dermatitis, n (%) l | 75 (52.08) |
miRNA | Phenotype Observed | p-Value | FDR a | FC or rho b |
---|---|---|---|---|
miR-1276 | Asthma | 4.511 × 10−4 | 0.032 | −2.136 |
miR-29B2 | Asthma | 7.260 × 10−4 | 0.040 | −1.334 |
miR-3175 | Asthma | 5.920 × 10−5 | 0.013 | −1.118 |
miR-33B | Asthma | 4.971 × 10−4 | 0.032 | −1.235 |
miR-4308 | Asthma | 5.039 × 10−4 | 0.032 | −1.856 |
miR-4523 | Asthma | 1.195 × 10−4 | 0.018 | −1.182 |
miR-4673 | Asthma | 2.164 × 10−4 | 0.024 | −2.020 |
miR-4785 | Asthma | 0.001 | 0.047 | −1.328 |
miR-590 | Asthma | 8.479 × 10−4 | 0.041 | −1.100 |
miR-638 | Asthma | 1.010 × 10−5 | 0.004 | −2.570 |
miR-614 | Atopic dermatitis | 1.190 × 10−6 | 5.239 × 10−4 | 1.847 |
miR-142 | IgE | 3.940 × 10−8 | 1.730 × 10−5 | 0.112 |
miR-3064 | IgE | 4.880 × 10−5 | 0.007 | 0.185 |
miR-4434 | IgE | 4.060 × 10−5 | 0.007 | 0.134 |
miR-1304 | PC20 | 1.920 × 10−6 | 8.428 × 10−4 | 0.105 |
miR-2355 | PC20 | 7.120 × 10−5 | 0.013 | 0.128 |
miR-26A2 | PC20 | 2.054 × 10−5 | 0.023 | 0.192 |
miR-645 | PC20 | 8.540 × 10−5 | 0.013 | 0.024 |
Pathway | Nb of Gene Targets | GWAS Associated Genes a | SLSJ Associated Genes a | |
---|---|---|---|---|
Negative correlation | Cell growth, division, differentiation and apoptosis | 64 | COL15A1, SOCS1, BCL2L1, DUSP2, SSR3 | COL15A1, SOCS1 |
Immune response | 33 | FER, IL6 | ||
Protein cleavage, biosynthesis and modification | 21 | BACE2 | ||
DNA and RNA synthesis and replication | 19 | MAT2A | ||
Aldehyde transport and reactions | 2 | DCAKD | ||
Positive correlation | Cell growth, division, differentiation and apoptosis | 158 | APC, CASP8, CRK, DUSP2, FOS, FRS2, HSPA1B, PRKCD, RTF1, SKI, TGFBR1 | HSPA1B, HSPA6, YWHAZ |
Brain, neurotransmission and nervous system | 44 | ALDH1A2, CDC42 | ARHGEF1 | |
Immune response | 38 | REL, TNFA1P3 | CDNK1B, STAT3 | |
Protein cleavage, biosynthesis and modification | 35 | INO80, LRP3 | MMP9 | |
Hormonal regulation | 29 | NAB2, POU2F1 | LDB1, SP1 |
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Bélanger, É.; Madore, A.-M.; Boucher-Lafleur, A.-M.; Simon, M.-M.; Kwan, T.; Pastinen, T.; Laprise, C. Eosinophil microRNAs Play a Regulatory Role in Allergic Diseases Included in the Atopic March. Int. J. Mol. Sci. 2020, 21, 9011. https://doi.org/10.3390/ijms21239011
Bélanger É, Madore A-M, Boucher-Lafleur A-M, Simon M-M, Kwan T, Pastinen T, Laprise C. Eosinophil microRNAs Play a Regulatory Role in Allergic Diseases Included in the Atopic March. International Journal of Molecular Sciences. 2020; 21(23):9011. https://doi.org/10.3390/ijms21239011
Chicago/Turabian StyleBélanger, Émile, Anne-Marie Madore, Anne-Marie Boucher-Lafleur, Marie-Michelle Simon, Tony Kwan, Tomi Pastinen, and Catherine Laprise. 2020. "Eosinophil microRNAs Play a Regulatory Role in Allergic Diseases Included in the Atopic March" International Journal of Molecular Sciences 21, no. 23: 9011. https://doi.org/10.3390/ijms21239011