Retrospective Study
Copyright ©The Author(s) 2019.
World J Gastroenterol. Oct 14, 2019; 25(38): 5850-5861
Published online Oct 14, 2019. doi: 10.3748/wjg.v25.i38.5850
Table 1 Characteristics of the 411 Crohn’s disease patients included in this study
CharacteristicAll patientsWith leukopeniaWithout leukopeniaP value
No. of subjects (%)41172 (17.5)339 (82.5)-
Gender
Male, n (%)305 (74.0)52 (17.0)253 (83.0)0.180
Female, n (%)106 (26.0)20 (18.9)86 (81.1)
NUDT15 R139C
CC, n (%)342 (80.4)35 (10.2)307 (89.8)2.40 × 10-15
CT, n (%)65 (17.9)33 (50.2)32 (49.8)
TT, n (%)4 (1.7)4 (100)0
TPMT*3C0.26
AA, n (%)398 (96.8)68 (17.1)330 (82.9)
AG, n (%)13 (3.2)4 (30.8)9 (69.2)
Age in years, median (range)28 (12-70)26(12-70)27(12-60)0.734
Medication
Azathiopurine337 (82.0)57 (17.3)273 (82.7)0.113
Mercaptopurine74 (18.0)14 (18.9)60 (81.1)
Thiopurines dose, mg/kg per day, median (range)1.7 (0.2-3.1)1.5 (0.5-2.6)1.7 (0.2-3.1)0.030
CD
Ileal L1346280.495
Colorectal L221615
Ileocolonic L329248244
Upper gastrointestinal L4611249
Co-medication211451660.74
Corticosteroids791564
Thalidomide511338
Anti-TNF agent641351
5-ASA404
Allopurinol1349
Table 2 Relationship between concentrations of 6-thioguanine nucleotide and thiopurine-induced leukopenia in different nucleoside diphosphate-linked moiety X-type motif 15 R139C genotype groups among 411 patients according to receiver operating characteristic curves
NUDT15 genotype (No. of patients)6TGNs (pmol/8 × 108 RBC)P valueAUC95%CISensitivity (%)Specificity (%)
CT + CC≥ 474.70.0710.57(0.49-0.65)34.782.6
CC (342)< 474.79.4 × 10-5(0.61-0.79)60.073.3
≥ 411.50.70
< 411.5
CT (65)≥ 319.20.0390.65(0.51-0.79)42.496.9
< 319.2
Table 3 Multivariable prediction model for thiouprine-induced leukopenia, including the nucleoside diphosphate-linked moiety X-type motif 1 R139C genotypes and 6-thioguanine nucleotide cut off levels
CategoryLeukopenia
% of totalOR (95%CI)P value
YesNo
NUDT15 R139C TT404/4 (100%)↑↑↑-
NUDT15 R139C CT + 6TGN > 319.214114/15 (93.3%)225.0 (27.6-1836.2)1.5 × 10-14
NUDT15 R139C CT + 6TGN < 319.2193119/50 (38.0%)9.9 (4.5-21.6)8.1 × 10-11
NUDT15 R139C CC + 6TGN > 411.5218221/103 (20.4%)4.1 (2.0-8.5)4.8 × 10-5
NUDT15 R139C CC + 6TGN < 411.51422514/239 (5.9%)Reference-
Total7233972/411 (17.5%)