Table 1.
Associations between genotypes of codon 139 and adverse events associated with thiopurines
| Codon 139 genotypea | Arg/Arg | Arg/Cys | Cys/Cys | p valuesb | Allelic associationc (Arg vs. Cys) | |
|---|---|---|---|---|---|---|
| p values | OR (95% CI) | |||||
| Number of subjects | 958 | 275 | 49 | |||
| All adverse events of thiopurines | 260 (27.1%) | 141 (51.3%) | 49 (100.0%) | 1.29E−32 | 1.55E−36 | 4.13 (3.28–5.20) |
| Leukopenia | 94 (9.8%) | 94 (34.2%) | 45 (91.8%) | 2.00E−56 | 2.20E−63 | 6.59 (5.19–8.36) |
| Severe (WBC < 2000/μL) | 17 (1.8%) | 33 (12.0%) | 38 (77.6%) | 3.09E−67 | 2.56E−75 | 13.1 (9.41–18.2) |
| Acute (< 8 weeks) | 14 (1.5%) | 27 (9.8%) | 39 (79.6%) | 7.06E−73 | 1.70E−80 | 15.6 (11.0–22.1) |
| Acute and severe | 3 (0.3%) | 11 (4.0%) | 33 (67.3%) | 2.62E−72 | 4.23E−80 | 34.2 (20.0–58.7) |
| Alopecia | 28 (2.9%) | 13 (4.7%) | 46 (93.9%) | 3.48E−62 | 1.32E−69 | 12.1 (8.67–16.8) |
| Severe (objective) | 1 (0.1%) | 3 (1.1%) | 44 (89.8%) | 8.51E−101 | 6.61E−113 | 141 (56.9–350) |
| Mild (self-reported) | 27 (2.8%) | 10 (3.6%) | 2 (4.1%) | 4.17E−01 | 4.83E−01 | |
| Liver dysfunction | 38 (4.0%) | 8 (2.9%) | 1 (2.0%) | 3.04E−01 | 3.44E−01 | |
| Pancreatitis | 18 (1.9%) | 2 (0.7%) | 0 (0.0%) | 1.06E−01 | 1.34E−01 | |
| Digestive symptoms | 55 (5.7%) | 31 (11.3%) | 6 (12.2%) | 9.55E−04 | 6.39E−04 | 1.89 (1.32–2.72) |
| Infection | 11 (1.1%) | 4 (1.5%) | 2 (4.1%) | 1.61E−01 | 2.11E−01 | |
| Fever | 10 (1.0%) | 3 (1.1%) | 0 (0.0%) | 6.82E−01 | 8.75E−01 | |
| Skin symptom | 5 (0.5%) | 2 (0.7%) | 0 (0.0%) | 9.79E−01 | 1.00 | |
| Malignant tumor | 1 (0.1%) | 0 (0.0%) | 1 (2.0%) | 5.91E−02 | 1.93E−01 | |
aRare genotypes (CH and RH) were excluded
bCochran–Armitage trend analysis
cChi-squared test