Influence of NUDT15 variants on hematological pictures of patients with inflammatory bowel disease treated with thiopurines

Figure 1 Change of white blood cell counts (Group A, B and C vs D). A: Absolute number of WBC counts in two groups (Groups A, B and C vs D). WBC gradually decreased after the thiopurine was started in both the mutant (n = 24) and the wild type. The WBC count of the mutant was lower and statistically significant at 6, 8, 10 and 16 wk (P = 0.0271, 0.0037, 0.0051 and 0.0185, respectively); B: Decrease rate of the WBC counts in two groups (Groups A, B and C vs D). The decrease rate was higher in the variants (n = 24) than the wild (n = 72) and statistically significant at 4, 6, 8, 10, 12, 14 and 16 wk (P = 0.004, 0.0001, 0.0012, 0.0022, 0.00001, 0.0264 and 0.0031, respectively). We set 1.0 as the WBC count at the beginning of thiopurines. WBC: White blood cell.

Figure 2 Change of white blood cell counts with or without prednisolone. A: Absolute number of WBC counts in two groups (Groups A + B + C vs D) with PSL. In the cases with prednisolone, WBC count tended to decreased more in the mutant cases (Group A + B + C) and was significantly different at 8 and 10 wk (P = 0.012 and 0.029, respectively); B: Absolute number of WBC counts in two groups (Groups A + B + C vs D) without PSL. In the cases without prednisolone, WBC count was significantly lower at 2, 4, 8 and 14 wk significantly in the mutant (Group A + B + C) than the wild cases (Group D, P = 0.0196, 0.0182, 0.0237 and 0.0241, respectively). PSL: Prednisolone; WBC: White blood cell.

Figure 3 Effect of thiopurine on white blood cell count. A: Absolute number of WBC counts in three groups (Groups A + B vs C vs D) without PSL. We next divided cases into 3 categories: Group A + B, Group C and Group D. Group C was already reported cases with NUDT15 c.415C>T in exon 3 in IBD cases. Group A + B included mutations in exon 1 which is not investigated in IBD. Group A + B and Group C was lower in WBC count and decrease rate than Group D; B: Decrease ratio of WBC counts in three groups (Groups A + B vs C vs D) without PSL; Group A + B and Group C was lower in WBC count and decrease rate than Group D; Group A + B and Group C was lower in decrease rate than Group D. PSL: Prednisolone; WBC: White blood cell; IBD: Inflammatory bowel disease.

Figure 4 Effect of thipourine on mean corpuscular volume. A: MCV in Groups A + B + C vs D. MCV increased after starting 6MP in both the mutant (Group A + B + C) and the wild cases (Group D, Figure 4). MCV was significantly higher at 10 wk in the mutant than the wild cases (P = 0.0085); B: Increase ratio of MCV in Groups A + B + C vs D. The increase rate was higher in the variants than the wild and statistically significant at 16 wk (P = 0.00198). We set 1.0 as the MCV at the beginning of thiopurines. 6MP: 6-mercaptopurine; MCV: Mean corpuscular volume.