A Pharmacogenetics Study in Mozambican Patients Treated with Nevirapine: Full Resequencing of TRAF3IP2 Gene Shows a Novel Association with SJS/TEN Susceptibility
Abstract
:1. Introduction
2. Results
Clinical Characteristics at Baseline | SJS | Controls | All | p (SJS/TEN vs. Controls) |
---|---|---|---|---|
Age, years | 31 (27–36) | 32 (27–36) | 32 (27–36) | 0.8 |
Viral load, log copies/mL | 4.1 (3.2–4.6) | 3.58 (2.39–4.43) | 3.72 (2.98–4.49) | 0.41 |
CD4 cell count, median cells/mm3 | 467 (326–721) | 393 (227–591) | 409 (230–634) | 0.21 |
BMI | 22.8 (21.5–25.4) | 22.8 (21.6–26.3) | 22.8 (21.6–25.9) | 0.78 |
ALT baseline U/L | 8.6 (6.9–12.8) | 10.7 (7.3–15.4) | 10.2 (7.1–15.2) | 0.28 |
AST baseline U/L | 20.5 (15.9–23.5) | 20.3 (16.9–23.6) | 20.4 (16.8–23.6) | 0.91 |
SNP | SNP Location | Cases/Controls | N | Genotypes * | p § | OR § (95% CI) | Alleles | p | OR (95% CI) | |||
---|---|---|---|---|---|---|---|---|---|---|---|---|
wt | hz | var | Wildtype | Variant | ||||||||
rs76228616 G>C | Exon 2 | SJS/TEN | 27 | 19 | 7 | 1 | 0.027 | 3.6 (1.2–10.95) | 45 | 9 | 0.012 | 3.65 (1.33–10.01) |
Controls | 77 | 69 | 8 | 0 | 146 | 8 | ||||||
rs33980500 G>A | Exon 3 | SJS/TEN | 27 | 20 | 5 | 2 | 0.25 | 1.93 (0.67–5.54) | 45 | 9 | 0.12 | 2.2 (0.88–5.49) |
Controls | 78 | 66 | 11 | 1 | 143 | 13 | ||||||
rs149246847 A>C | SJS/TEN | 22 | 22 | 0 | 0 | 0.55 | ND | 44 | 0 | 0.55 | ND | |
Controls | 50 | 47 | 3 | 0 | 97 | 3 | ||||||
rs13190932 C>T | SJS/TEN | 27 | 25 | 2 | 0 | 1 | 0.81 (0.16–4.17) | 52 | 2 | 1 | 0.82 (0.16–4.07) | |
Controls | 78 | 71 | 7 | 0 | 149 | 7 | ||||||
rs113085690 T>C | Intron 6 | SJS/TEN | 27 | 27 | 0 | 0 | 1 | ND | 30 | 0 | 1 | ND |
Controls | 50 | 49 | 1 | 0 | 55 | 1 | ||||||
rs115622353 C>G | Exon 7 | SJS/TEN | 27 | 26 | 1 | 0 | 0.65 | 0.44 (0.05–4.17) | 53 | 1 | 0.66 | 0.45 (0.05–4.16) |
Controls | 50 | 46 | 4 | 0 | 96 | 4 | ||||||
rs34659678 G>A | SJS/TEN | 25 | 25 | 0 | 0 | 0.29 | ND | 50 | 0 | 0.3 | ND | |
Controls | 50 | 46 | 4 | 0 | 96 | 4 | ||||||
rs112619881 G>A | SJS/TEN | 26 | 24 | 2 | 0 | 0.49 | 0.51 (0.1–2.66) | 50 | 2 | 0.5 | 0.53 (0.11–2.7) | |
Controls | 50 | 43 | 7 | 0 | 93 | 7 | ||||||
rs2280985 T>C | Intron 9 | SJS/TEN | 27 | 25 | 2 | 0 | 1 | 0.69 (0.12–3.8) | 52 | 2 | 1 | 0.7 (0.13–3.74) |
Controls | 48 | 43 | 5 | 0 | 91 | 5 | ||||||
rs6912112 T>C | SJS/TEN | 27 | 12 | 11 | 4 | 0.54 | 1.32 (0.54–3.17) | 35 | 19 | 0.39 | 1.38 (0.72–2.67) | |
Controls | 78 | 40 | 32 | 6 | 112 | 44 | ||||||
rs138485893 T>C | Exon 10 | SJS/TEN | 27 | 27 | 0 | 0 | 0.57 | ND | 54 | 0 | 0.57 | ND |
Controls | 78 | 75 | 3 | 0 | 153 | 3 |
Variables | B | p | OR (95% CI) | R2 (Cox and Snell) |
---|---|---|---|---|
age | 0.065 | 0.142 | 1.07 (0.98–1.16) | 0.246 |
Viral load (baseline) | 0.00 | 0.311 | 1.00 | |
BMI | 0.017 | 0.815 | 1.02 (0.88–1.17) | |
CD4_50 (baseline) | 0.111 | 0.083 | 1.12 (0.99–1.27) | |
TRAF3IP2 rs76228616 | 1.479 | 0.027 | 4.39 (1.19–16.23) | |
CYP2B6 rs3745274 | 1.147 | 0.006 | 3.15 (1.38–7.19) | |
CYP2B6 rs28399499 | 1.579 | 0.011 | 4.85 (1.43–16.4) | |
HCP5 rs3099844 | 0.595 | 0.158 | 1.81 (0.79–4.14) |
CYP2B6 rs28399499 | |||||
---|---|---|---|---|---|
TT | TC + CC | ||||
SJS/TEN | Controls | SJS/TEN | Controls | ||
TRAF3IP2 rs76228616 | GG | 13 | 61 | 6 | 8 |
GC + CC | 7 | 8 | 1 | 0 |
3. Discussion
4. Experimental Section
4.1. Patients
4.2. Genotyping and Statistical Analysis
Supplementary Materials
Author Contributions
Conflicts of Interest
References
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Ciccacci, C.; Rufini, S.; Mancinelli, S.; Buonomo, E.; Giardina, E.; Scarcella, P.; Marazzi, M.C.; Novelli, G.; Palombi, L.; Borgiani, P. A Pharmacogenetics Study in Mozambican Patients Treated with Nevirapine: Full Resequencing of TRAF3IP2 Gene Shows a Novel Association with SJS/TEN Susceptibility. Int. J. Mol. Sci. 2015, 16, 5830-5838. https://doi.org/10.3390/ijms16035830
Ciccacci C, Rufini S, Mancinelli S, Buonomo E, Giardina E, Scarcella P, Marazzi MC, Novelli G, Palombi L, Borgiani P. A Pharmacogenetics Study in Mozambican Patients Treated with Nevirapine: Full Resequencing of TRAF3IP2 Gene Shows a Novel Association with SJS/TEN Susceptibility. International Journal of Molecular Sciences. 2015; 16(3):5830-5838. https://doi.org/10.3390/ijms16035830
Chicago/Turabian StyleCiccacci, Cinzia, Sara Rufini, Sandro Mancinelli, Ersilia Buonomo, Emiliano Giardina, Paola Scarcella, Maria C. Marazzi, Giuseppe Novelli, Leonardo Palombi, and Paola Borgiani. 2015. "A Pharmacogenetics Study in Mozambican Patients Treated with Nevirapine: Full Resequencing of TRAF3IP2 Gene Shows a Novel Association with SJS/TEN Susceptibility" International Journal of Molecular Sciences 16, no. 3: 5830-5838. https://doi.org/10.3390/ijms16035830
APA StyleCiccacci, C., Rufini, S., Mancinelli, S., Buonomo, E., Giardina, E., Scarcella, P., Marazzi, M. C., Novelli, G., Palombi, L., & Borgiani, P. (2015). A Pharmacogenetics Study in Mozambican Patients Treated with Nevirapine: Full Resequencing of TRAF3IP2 Gene Shows a Novel Association with SJS/TEN Susceptibility. International Journal of Molecular Sciences, 16(3), 5830-5838. https://doi.org/10.3390/ijms16035830