A Novel Smad7 Genetic Variant Mapping on the Genomic Region Targeted by Mongersen Is Associated with Crohn’s Disease
Abstract
:1. Introduction
2. Experimental Section
2.1. Study Population
2.2. DNA Extraction and Genotyping
2.3. PBMCs Isolation and Culture
2.4. Assessment of Cell Death
2.5. RNA Extraction and Real-Time PCR
2.6. Statistical Analysis
3. Results
3.1. Frequency of Variant Allele of rs144204026 in CD
3.2. Relationship between Frequency of the T Variant Allele and the Demographic/Clinical Characteristic of CD Patients
3.3. Mongersen Down-Regulates Smad7 in PBMCs of Individuals Carrying T Variant Allele
4. Discussion
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Diagnosis | CD_1 N (%) | UC_1 N (%) | CD_2 N (%) | UC_2 N (%) | CD_Tot N (%) | UC_Tot N (%) |
---|---|---|---|---|---|---|
N | 235 | 198 | 122 | 142 | 357 | 340 |
Gender Female | 123 (52.3) | 86 (43.4) | 49 (40.2) | 49 (34.5) | 172 (48.2) | 135 (39.7) |
Mean Age | 48 | 55 | 51 | 51 | 50 | 52 |
Smoking habit | ||||||
Current | 64 (27.2) | 24 (12.1) | 18 (14.8) | 2 (1.4) | 82 (23) | 26 (7.6) |
Former | 47 (20) | 44 (22.2) | 13 (10.7) | 15 (10.6) | 60 (16.8) | 59 (17.4) |
Family history of IBD | 48 (20.4) | 27 (13.6) | 7 (5.7) | 3 (2.1) | 55 (15.4) | 30 (8.8) |
CD location * | ||||||
Ileum | 136 (57.9) | - | 39 (32) | - | 175 (49) | - |
Colon | 15 (6.4) | - | 19 (15.6) | - | 34 (9.5) | - |
Ileo-colon | 64 (27.2) | - | 64 (52.5) | - | 128 (35.9) | - |
Isolated upper disease | 5 (2.1) | - | 5 (1.4) | - | ||
CD behaviour ** | ||||||
Non-structuring/ Non-penetrating | 63 (26.8) | - | 60 (49.2) | - | 123 (34.5) | - |
Stricturing | 100 (42.6) | - | 26 (21.3) | - | 126 (35.3) | - |
Penetrating | 57 (24.3) | - | 23 (18.9) | - | 80 (22.4) | - |
Perianal disease | 73 (31.1) | - | 22 (18.0) | - | 95 (26.6) | - |
Colitis extent *** | ||||||
Distal | - | 95 (47.9) | - | 49 (34.5) | - | 144 (42.3) |
Left sided | - | 28 (14.1) | - | 38 (26.7) | - | 66 (19.4) |
Extensive | - | 60 (30.3) | - | 55 (38.7) | - | 115 (33.8) |
Controls N = 363 (%) | CD_1 N = 235 (%) | UC_1 N = 198 (%) | CD_2 N = 122 (%) | UC_2 N = 142 (%) | CD_Tot N = 357 (%) | UC_Tot N = 340 (%) | |
---|---|---|---|---|---|---|---|
CC | 357 (98.3) | 224 (95.3) | 191 (96.5) | 114 (93.4) | 137 (96.5) | 338 (94.7) | 328 (96.5) |
CT | 6 (1.7) | 11 (4.7) | 7 (3.5) | 8 (6.6) | 5 (3.5) | 19 (5.3) | 12 (3.5) |
TT | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
p = 0.029 | p = 0.15 | p = 0.01 | p = 0.19 | p = 0.007 | p = 0.11 |
Controls N = 726 (%) | CD_Tot N = 714 (%) | UC_Tot N = 680 (%) | |
---|---|---|---|
C | 720 (99.2) | 695 (97.3) | 668 (98.2) |
T | 6 (0.8) | 19 (2.7) | 12 (1.7) |
p = 0.008 OR = 3.28 (1.3–8.3) | p = 0.12 OR = 2.16 (0.8–5.8) |
Diagnosis | CC N = 338 (%) | CT N = 19 (%) | p Value |
---|---|---|---|
Gender Female | 163 (48.2) | 10 (55.5) | p = 0.54 |
Mean Age | 50 | 50 | |
Smoking habit | |||
Current | 78 (23.1) | 4 (22.2) | p = 0.93 |
Former | 57 (16.9) | 3 (16.7) | p = 0.98 |
Family history of IBD | 52 (15.4) | 3 (16.7) | |
CD location * | |||
Ileum | 166 (49) | 9 (50) | p = 0.94 |
Colon | 33 (9.5) | 1 (5.6) | p = 0.55 |
Ileo-colon | 120 (35.9) | 8 (44.4) | p = 0.44 |
Isolated upper disease | 5 (1.4) | - | |
CD behaviour ** | |||
Non structuring/ Non penetrating | 116 (34.5) | 7 (38.9) | p = 0.69 |
Stricturing | 121 (35.3) | 5 (27.8) | p = 0.48 |
Penetrating | 74 (22.4) | 6 (33.3) | p = 0.25 |
Perianal disease | 92 (27.2) | 3 (16.7) | p = 0.32 |
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Di Fusco, D.; Marafini, I.; Stolfi, C.; Troncone, E.; Onali, S.; Lolli, E.; Caprioli, F.; Mazza, S.; Raffaella, C.; Manzo, L.; et al. A Novel Smad7 Genetic Variant Mapping on the Genomic Region Targeted by Mongersen Is Associated with Crohn’s Disease. Biomedicines 2020, 8, 234. https://doi.org/10.3390/biomedicines8080234
Di Fusco D, Marafini I, Stolfi C, Troncone E, Onali S, Lolli E, Caprioli F, Mazza S, Raffaella C, Manzo L, et al. A Novel Smad7 Genetic Variant Mapping on the Genomic Region Targeted by Mongersen Is Associated with Crohn’s Disease. Biomedicines. 2020; 8(8):234. https://doi.org/10.3390/biomedicines8080234
Chicago/Turabian StyleDi Fusco, Davide, Irene Marafini, Carmine Stolfi, Edoardo Troncone, Sara Onali, Elisabetta Lolli, Flavio Caprioli, Stefano Mazza, Cascella Raffaella, Laura Manzo, and et al. 2020. "A Novel Smad7 Genetic Variant Mapping on the Genomic Region Targeted by Mongersen Is Associated with Crohn’s Disease" Biomedicines 8, no. 8: 234. https://doi.org/10.3390/biomedicines8080234