Gene Variants in Components of the microRNA Processing Pathway in Chronic Myeloid Leukemia
Abstract
:1. Introduction
2. Material and Methods
2.1. Study Population
2.2. Gene Variant Genotyping
2.3. Statistical Analysis
3. Results
3.1. Characteristics of the Study Population
3.2. Gene Variants in Components of miRNA Biosynthesis Pathway and CML
3.3. Association of Variants in Components of miRNA Biogenesis with Prognostic Scores and Age at Diagnosis in CML
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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CML n = 296 (%) | Controls n = 485 (%) | |
---|---|---|
Age, median ± SD | 45 ± 14.7 | 48 ± 7.4 |
Males | 170 (57%) | 271 (56%) |
Females | 126 (43%) | 214 (44%) |
Sokal Score (n = 118) | ||
HR | 52 (44%) | - |
IR | 34 (29%) | - |
LR | 32 (27%) | - |
Hasford Score (n = 118) | ||
HR | 48 (41%) | - |
IR | 36 (30%) | - |
LR | 34 (29%) | - |
EUTOS Score (n = 97) | ||
HR | 50 (52%) | - |
LR | 47 (48%) | - |
Gene | SNV | Alleles | Cases Freq (n) | Controls Freq (n) | p-Value | OR (CI 95%) |
---|---|---|---|---|---|---|
GEMIN3 | rs197388 | A | 0.92 (538) | 0.91 (878) | ||
T | 0.08 (46) | 0.09 (84) | 0.557 | 0.89 (0.614–1.301) | ||
DROSHA | rs10719 | G | 0.67 (396) | 0.65 (628) | ||
A | 0.33 (196) | 0.35 (342) | 0.385 | 0.91 (0.732–1.128) | ||
rs6877842 | G | 0.90 (535) | 0.90 (874) | |||
C | 0.10 (57) | 0.10 (96) | 0.862 | 0.97 (0.687–1.370) | ||
XPO5 | rs11077 | T | 0.61 (358) | 0.63 (614) | ||
G | 0.39 (232) | 0.37 (356) | 0.300 | 1.12 (0.905–1.382) | ||
rs34324334 | C | 0.94 (556) | 0.93 (906) | |||
T | 0.06 (36) | 0.07 (64) | 0.685 | 0.92 (0.601–1.397) | ||
AGO2 | rs2293939 | G | 0.78 (463) | 0.79 (764) | ||
A | 0.22 (129) | 0.21 (204) | 0.737 | 1.04 (0.813–1.338) | ||
rs4961280 | C | 0.67 (397) | 0.63 (607) | |||
A | 0.33 (193) | 0.37 (363) | 0.059 | 0.81 (0.655–1.009) | ||
DICER | rs3742330 | A | 0.83 (492) | 0.82 (797) | ||
G | 0.17 (98) | 0.18 (173) | 0.535 | 0.92 (0.699–1.205) | ||
rs13078 | T | 0.91 (539) | 0.94 (915) | |||
A | 0.09 (53) | 0.06 (55) | 0.013 | 1.64 (1.105–2.421) | ||
GEMIN4 | rs7813 | A | 0.70 (414) | 0.71 (685) | ||
G | 0.30 (178) | 0.29 (285) | 0.773 | 1.03 (0.826–1.292) | ||
rs2740349 | T | 0.81 (477) | 0.80 (776) | |||
C | 0.19 (115) | 0.20 (194) | 0.782 | 0.96 (0.745–1.247) | ||
DGCR8 | rs720012 | G | 0.57 (334) | 0.55 (533) | ||
A | 0.43 (256) | 0.45 (437) | 0.521 | 0.93 (0.760–1.149) | ||
TNRC6B | rs9611280 | G | 0.98 (578) | 0.97 (937) | ||
A | 0.02 (14) | 0.03 (33) | 0.244 | 0.69 (0.364–1.296) |
Gene | SNV | Alleles | Genotype | Cases Freq (n) | Controls Freq (n) | p-Value | OR (CI 95%) |
---|---|---|---|---|---|---|---|
GEMIN3 | rs197388 | A/T | AA | 0.86 (250) | 0.84 (404) | ||
AT | 0.13 (38) | 0.15 (70) | 0.546 | 0.88 (0.569–1.339) | |||
TT | 0.01 (4) | 0.01 (7) | 1.00 | 0.94 (0.235–3.220) | |||
DROSHA | rs10719 | G/A | GG | 0.45 (134) | 0.43 (208) | ||
GA | 0.43 (128) | 0.44 (212) | 0.680 | 0.94 (0.688–1.277) | |||
AA | 0.12 (34) | 0.13 (65) | 0.383 | 0.81 (0.505–1.294) | |||
rs6877842 | G/C | GG | 0.811 (240) | 0.82 (396) | |||
GC | 0.186 (55) | 0.17 (82) | 0.598 | 1.11 (0.756–1.612) | |||
CC | 0.003 (1) | 0.01 (7) | 0.269 | 0.26 (0.010–1.540) | |||
XPO5 | rs11077 | T/G | TT | 0.37 (108) | 0.41 (197) | ||
TG | 0.48 (142) | 0.45 (220) | 0.310 | 1.18 (0.859–1.616) | |||
GG | 0.15 (45) | 0.14 (68) | 0.406 | 1.21 (0.771–1.880) | |||
rs34324334 | C/T | CC | 0.89 (263) | 0.87 (424) | |||
CT | 0.10 (30) | 0.12 (58) | 0.445 | 0.84 (0.518–1.326) | |||
TT | 0.01 (3) | 0.01 (3) | 0.680 | 1.61 (0.276–9.437) | |||
AGO2 | rs2293939 | G/A | GG | 0.62 (183) | 0.62 (301) | ||
GA | 0.33 (97) | 0.34 (162) | 0.924 | 0.99 (0.720–1.344) | |||
AA | 0.05 (16) | 0.04 (21) | 0.512 | 1.26 (0.627–2.470) | |||
rs4961280 | C/A | CC | 0.47 (138) | 0.40 (193) | |||
CA | 0.41 (121) | 0.45 (221) | 0.0925 | 0.77 (0.561–1.046) | |||
AA | 0.12 (36) | 0.15 (71) | 0.139 | 0.71 (0.446–1.117) | |||
DICER1 | rs3742330 | A/G | AA | 0.69 (205) | 0.68 (329) | ||
AG | 0.28 (82) | 0.29 (139) | 0.741 | 0.95 (0.683–1.308) | |||
GG | 0.03 (8) | 0.03 (17) | 0.520 | 0.76 (0.303–1.763) | |||
rs13078 | T/A | TT | 0.855 (253) | 0.889 (431) | |||
TA | 0.111 (33) | 0.109 (53) | 0.802 | 1.06 (0.663–1.679) | |||
AA | 0.034 (10) | 0.002 (1) | 0.0004 | 15.06 (2.824–373.6) | |||
GEMIN4 | rs7813 | A/G | AA | 0.51 (150) | 0.50 (244) | ||
AG | 0.38 (114) | 0.41 (197) | 0.70 | 0.94 (0.691–1.280) | |||
GG | 0.11 (32) | 0.09 (44) | 0.509 | 1.18 (0.713–1.947) | |||
rs2740349 | T/C | TT | 0.66 (196) | 0.65 (313) | |||
TC | 0.29 (85) | 0.31 (150) | 0.541 | 0.91 (0.656–1.246) | |||
CC | 0.05 (15) | 0.04 (22) | 0.806 | 1.09 (0.540–2.150) | |||
DGCR8 | rs720012 | G/A | GG | 0.33 (97) | 0.31 (149) | ||
GA | 0.47 (140) | 0.48 (235) | 0.599 | 0.92 (0.658–1.275) | |||
AA | 0.20 (58) | 0.21 (101) | 0.551 | 0.88 (0.583–1.332) | |||
TNRC6B | rs9611280 | G/A | GG | 0.95 (282) | 0.93 (452) | ||
GA | 0.05 (14) | 0.07 (33) | 0.237 | 0.68 (0.348–1.280) | |||
AA | 0 (0) | 0 (0) | NA | NA |
Gene/SNV | Allele | Sokal | Hasford | Eutos | ||||||
---|---|---|---|---|---|---|---|---|---|---|
HR n = 52 | LR-IR n = 66 | OR | HR n = 48 | LR-IR n = 70 | OR | HR n = 50 | LR n = 47 | OR | ||
GEMIN3 rs197388 | T | 0.08 | 0.05 | 1.83 | 0.07 | 0.04 | 1.77 | 0.08 | 0.04 | 2.00 |
DROSHA rs10719 rs6877842 | ||||||||||
A | 0.28 | 0.36 | 0.7 | 0.27 | 0.34 | 0.71 | 0.28 | 0.36 | 0.68 | |
C | 0.12 | 0.08 | 1.44 | 0.11 | 0.09 | 1.38 | 0.10 | 0.09 | 1.07 | |
XPO5 rs11077 rs34324334 | ||||||||||
G | 0.44 | 0.36 | 1.39 | 0.47 | 0.36 | 1.54 | 0.42 | 0.42 | 1.01 | |
T | 0.06 | 0.03 | 1.96 | 0.04 | 0.04 | 0.97 | 0.05 | 0.05 | 0.96 | |
AGO2 rs2293939 rs4961280 | ||||||||||
A | 0.2 | 0.2 | 1.03 | 0.21 | 0.19 | 1.10 | 0.21 | 0.18 | 1.24 | |
A | 0.37 | 0.33 | 1.15 | 0.33 | 0.37 | 0.85 | 0.34 | 0.40 | 0.79 | |
DICER1 rs3742330 rs13078 | ||||||||||
G | 0.13 | 0.17 | 0.78 | 0.15 | 0.16 | 0.92 | 0.16 | 0.17 | 0.95 | |
A | 0.08 | 0.11 | 0.7 | 0.09 | 0.09 | 1.01 | 0.09 | 0.09 | 0.96 | |
GEMIN4 rs7813 rs2740349 | ||||||||||
G | 0.36 | 0.26 | 1.59 | 0.39 | 0.24 | 1.96 * | 0.35 | 0.26 | 1.53 | |
C | 0.25 | 0.17 | 1.67 | 0.27 | 0.14 | 2.23 ** | 0.23 | 0.17 | 1.49 | |
DGCR8 rs720012 | A | 0.6 | 0.56 | 1.16 | 0.59 | 0.55 | 1.20 | 0.58 | 0.56 | 1.07 |
TNRC6B rs9611280 | A | 0.02 | 0.02 | 0.84 | 0.03 | 0.01 | 2.23 | 0.02 | 0.02 | 0.96 |
Gene | SNV | Minor Allele | p-Value | β | CI 95% |
---|---|---|---|---|---|
GEMIN3 | rs197388 | T | 0.705 | −1.077 | (−6.64–4.48) |
DROSHA | rs10719 | A | 0.544 | −0.9741 | (−4.11–2.16) |
rs6877842 | C | 0.926 | 0.2497 | (−5.02–5.52) | |
XPO5 | rs11077 | G | 0.306 | −1.564 | (−4.55–1.42) |
rs34324334 | T | 0.557 | −1.841 | (−7.97–4.29) | |
AGO2 | rs2293939 | A | 0.678 | 0.788 | (−2.93–4.51) |
rs4961280 | A | 0.781 | −0.4242 | (−3.41–2.56) | |
DICER1 | rs3742330 | G | 0.460 | −1.554 | (−5.67–2.56) |
rs13078 | A | 0.162 | 3.106 | (−1.23–7.45) | |
GEMIN4 | rs7813 | G | 0.059 | 2.955 | (−0.09–6.00) |
rs2740349 | C | 0.003 | 5.395 | (1.88–8.91) | |
DGCR8 | rs720012 | A | 0.296 | −1.589 | (−4.56–1.38) |
TNRC6B | rs9611280 | A | 0.301 | 5.233 | (−4.66–15.12) |
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Chavaro-Francisco, G.; Hernández-Zavala, A.; Bravo-Cidro, C.E.; Rios-Rodriguez, S.; Muciño-Sánchez, M.; López-López, M.; Castro-Martínez, X.H.; Olarte-Carrillo, I.; Garcia-Laguna, A.; Barranco-Lampón, G.; et al. Gene Variants in Components of the microRNA Processing Pathway in Chronic Myeloid Leukemia. Genes 2024, 15, 1054. https://doi.org/10.3390/genes15081054
Chavaro-Francisco G, Hernández-Zavala A, Bravo-Cidro CE, Rios-Rodriguez S, Muciño-Sánchez M, López-López M, Castro-Martínez XH, Olarte-Carrillo I, Garcia-Laguna A, Barranco-Lampón G, et al. Gene Variants in Components of the microRNA Processing Pathway in Chronic Myeloid Leukemia. Genes. 2024; 15(8):1054. https://doi.org/10.3390/genes15081054
Chicago/Turabian StyleChavaro-Francisco, Guillermina, Araceli Hernández-Zavala, Camila E. Bravo-Cidro, Sandybel Rios-Rodriguez, Mabel Muciño-Sánchez, Marisol López-López, Xóchitl H. Castro-Martínez, Irma Olarte-Carrillo, Anel Garcia-Laguna, Gilberto Barranco-Lampón, and et al. 2024. "Gene Variants in Components of the microRNA Processing Pathway in Chronic Myeloid Leukemia" Genes 15, no. 8: 1054. https://doi.org/10.3390/genes15081054