Variants of MicroRNA Genes: Gender-Specific Associations with Multiple Sclerosis Risk and Severity
Abstract
:1. Introduction
2. Results
2.1. Analysis of Association of miRNA Genetic Variants with MS Susceptibility
Carriage of Allele/Genotype Combinations | Carriers (%)/Noncarriers (%) | Fisher’s pf-Value | Bonferroni-Corrected ‡ pcorr-Value | OR (95% CI) | |
---|---|---|---|---|---|
- | Without Gender Stratification | - | |||
MS Cases, n = 561 | Controls, n = 441 | ||||
MIR223*T # | 155 (27.6)/406 (72.4) | 86 (19.5)/355 (80.5) | 0.0017 | 0.0068 | 1.58 (1.17–2.13) |
MIR146A*G/G | 359 (64.0)/202 (36.0) | 268 (60.8)/173 (39.2) | 0.16 | 0.64 | 1.15 (0.89–1.48) |
MIR223*T + MIR146A*G/G | 103 (18.4)/458 (81.6) | 55 (12.5)/386 (87.5) | 0.0068 | 0.041 | 1.58 (1.11–2.25) |
- | Women | - | |||
MS Cases, n = 395 | Controls, n = 285 | ||||
MIR223*T | 122 (30.9)/273 (69.1) | 65 (22.8)/220 (77.2) | 0.012 | 0.048 | 1.51 (1.07–2.15) |
MIR146A*G/G | 259 (65.6)/136 (34.4) | 165 (57.9)/120 (42.1) | 0.025 | 0.10 | 1.39 (1.01–1.90) |
MIR223*T + MIR146A*G/G | 83 (21.0)/312 (79.0) | 37 (13.0)/248 (87.0) | 0.0042 | 0.025 | 1.79 (1.17–2.72) |
- | Men | - | |||
MS Cases, n = 166 | Controls, n = 149 | ||||
MIR223*T | 33 (19.9)/130 (80.1) | 21 (14.1)/128 (85.9) | 0.11 | 0.44 | 1.51 (0.83–2.75) |
MIR146A*G/G | 100 (60.3)/66 (39.7) | 98 (65.8)/51 (34.2) | 0.19 | 0.76 | 0.79 (0.50–1.25) |
MIR223*T + MIR146A*G/G | 20 (12.0)/146 (88.0) | 18 (12.1)/131 (87.9) | 0.56 | 1.00 | 1.00 (0.51–1.97) |
2.2. Analysis of Association of miRNA Genetic Variants with MS Severity
Characteristics | MS Patients, n = 561 | Women, n = 395 | Men, n = 166 |
---|---|---|---|
Age at onset (years), mean ± SD | 27.5 ± 9.2 | 27.9 ± 9.2 | 26.41 ± 9.2 |
Disease duration (years), mean ± SD | 11.3 ± 7.4 | 11.9 ± 7.8 | 10.1 ± 5.0 |
EDSS, mean ± SD | 2.48 ± 1.17 | 2.45 ± 1.13 | 2.54 ± 1.26 |
MSSS, mean ± SD | 3.93 ± 1.97 | 3.82 ± 1.97 † | 4.22 ± 1.96 † |
No. of persons with RRMS/SPMS | 464/97 | 329/66 | 135/31 |
Carriage of Allele/Genotype Combinations | Carriers (%)/Noncarriers (%) | Fisher’s p-Value | Bonferroni-Corrected ‡ p-Value | OR (95% CI) | |
---|---|---|---|---|---|
- | Without Gender Stratification | - | |||
MSSS > 3.5, n = 304 | MSSS ≤ 3.5, n = 242 | ||||
MIR499A*C/T | 112 (36.8)/192 (63.2) | 58 (24.0)/184 (76.0) | 0.00081 | 0.0032 | 1.85 (1.27–2.70) |
MIR499A*C # | 119 (39.1)/185 (60.9) | 69 (28.5)/173 (71.5) | 0.0059 | 0.024 | 1.61 (1.12–2.32) |
MIR499A*C/T + MIR196A2*C | 101 (33.2)/203 (66.8) | 46 (19.0)/196 (81.0) | 0.00013 | 0.00078 | 2.12 (1.42–3.16) |
MIR499A*C + MIR196A2*C | 107 (35.2)/197 (64.8) | 55 (22.7)/187 (77.3) | 0.00099 | 0.0059 | 1.85 (1.26–2.71) |
- | Women | - | |||
MSSS > 3.5, n = 207 | MSSS ≤ 3.5, n = 181 | ||||
MIR499A*C/T | 86 (41.5)/121 (58.5) | 37 (20.4)/144 (79.6) | 5.58 × 10−6 | 2.23 × 10−5 | 2.77 (1.76–4.36) |
MIR499A*C | 89 (43.0)/118 (57.0) | 46 (25.4)/135 (74.6) | 0.00020 | 0.00080 | 2.21 (1.44–3.41) |
MIR499A*C/T + MIR196A2*C | 79 (38.2)/128 (61.8) | 29 (16.0)/152 (84.0) | 7.38 × 10−7 | 4.43 × 10−6 | 3.23 (1.99–5.26) |
MIR499A*C + MIR196A2*C | 81 (39.1)/126 (60.9) | 37 (20.4)/144 (79.6) | 4.5 × 10−5 | 0.00027 | 2.50 (1.58–3.95) |
- | Men | - | |||
MSSS > 3.5, n = 97 | MSSS ≤ 3.5, n = 61 | ||||
MIR499A*C/T | 26 (26.8)/71 (73.2) | 21 (34.4)/40 (65.6) | 0.2 | 0.80 | 0.70 (0.35–1.40) |
MIR499A*C | 30 (30.9)/67 (69.1) | 23 (37.8)/38 (62.2) | 0.24 | 0.96 | 0.74 (0.38–1.45) |
MIR499A*C/T + MIR196A2*C | 7 (7.2)/90 (92.8) | 8 (13.1)/53 (86.9) | 0.17 | 1.00 | 0.52 (0.17–1.50) |
MIR499A*C + MIR196A2*C | 26 (26.8)/71 (73.2) | 18 (29.5)/43 (70.5) | 0.42 | 1.00 | 0.87 (0.43–1.78) |
Group of Patients | Carriers | Noncarriers | Mann-Whitney p-Value | ||||
---|---|---|---|---|---|---|---|
No. of Persons (%) | MSSS, Mean ± SD | No. of Persons (%) | MSSS, Mean ± SD | ||||
MIR499A*C/T | |||||||
All persons | 170 (31.1) | 4.23 ± 1.92 | 376 (68.9) | 3.80 ± 1.98 | 0.0085 | ||
Women | 123 (31.7) | 4.30 ± 1.97 | 265 (68.3) | 3.60 ± 1.93 | 0.0004 | ||
Men | 47 (29.7) | 4.04 ± 1.80 | 111 (70.3) | 4.30 ± 2.03 | 0.57 | ||
MIR499A*C | |||||||
All persons | 188 (34.4) | 4.16 ± 1.93 | 358 (65.6) | 3.81 ± 1.98 | 0.028 | ||
Women | 135 (34.8) | 4.19 ± 1.97 | 253 (65.2) | 3.62 ± 1.94 | 0.0039 | ||
Men | 53 (33.5) | 4.11 ± 1.85 | 105 (66.5) | 4.28 ± 2.02 | 0.70 | ||
MIR499A*C/T + MIR196A2*C | |||||||
All persons | 147 (26.9) | 4.27 ± 1.93 | 399 (73.1) | 3.81 ± 1.97 | 0.0062 | ||
Women | 108 (27.8) | 4.36 ± 1.96 | 280 (72.2) | 3.61 ± 1.93 | 0.0003 | ||
Men | 39 (24.7) | 4.04 ± 1.85 | 119 (75.3) | 4.28 ± 2.00 | 0.61 | ||
MIR499A*C + MIR196A2*C | |||||||
All persons | 162 (29.7) | 4.20 ± 1.96 | 384 (70.3) | 3.82 ± 1.97 | 0.023 | ||
Women | 118 (30.4) | 4.21 ± 1.98 | 270 (69.6) | 3.64 ± 1.94 | 0.0048 | ||
Men | 44 (27.8) | 4.17 ± 1.91 | 114 (72.2) | 4.24 ± 1.99 | 0.92 |
3. Discussion
4. Experimental Section
4.1. Patients and Controls
4.2. Genotyping
4.3. Statistical Analysis
5. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Kiselev, I.; Bashinskaya, V.; Kulakova, O.; Baulina, N.; Popova, E.; Boyko, A.; Favorova, O. Variants of MicroRNA Genes: Gender-Specific Associations with Multiple Sclerosis Risk and Severity. Int. J. Mol. Sci. 2015, 16, 20067-20081. https://doi.org/10.3390/ijms160820067
Kiselev I, Bashinskaya V, Kulakova O, Baulina N, Popova E, Boyko A, Favorova O. Variants of MicroRNA Genes: Gender-Specific Associations with Multiple Sclerosis Risk and Severity. International Journal of Molecular Sciences. 2015; 16(8):20067-20081. https://doi.org/10.3390/ijms160820067
Chicago/Turabian StyleKiselev, Ivan, Vitalina Bashinskaya, Olga Kulakova, Natalia Baulina, Ekaterina Popova, Alexey Boyko, and Olga Favorova. 2015. "Variants of MicroRNA Genes: Gender-Specific Associations with Multiple Sclerosis Risk and Severity" International Journal of Molecular Sciences 16, no. 8: 20067-20081. https://doi.org/10.3390/ijms160820067