Nucleoside diphosphate-linked moiety X-type motif 15 R139C genotypes impact 6-thioguanine nucleotide cut-off levels to predict thiopurine-induced leukopenia in Crohn’s disease patients

Figure 1 6-thioguanine nucleotide level and its ratio to thiopurine dose according to nucleoside diphosphate-linked moiety X-type motif 15 R139C diplotype. A: The level of 6-thioguanine nucleotide (6TGN) was much higher in the nucleoside diphosphate-linked moiety X-type motif 15 CC group than in the CT and TT groups [^bP < 0.01, 312.4 pmol/8 × 10⁸ red blood cells (RBC) vs 312.4 pmol/8 × 10⁸ RBC vs 135.8 pmol/8 × 10⁸ RBC]. B: There was no difference in the ratio of the level of 6TGN to the thiopurine dose among these three groups. 6TGN: 6-thioguanine nucleotide; RBC: Red blood cells.

Figure 2 Relationship between thiopurine-induced leukopenia and 6-thioguanine nucleotide concentrations in different nucleoside diphosphate-linked moiety X-type motif 15 R139C genotypes. In the CC group (n = 342), the median 6-thioguanine nucleotide (6TGN) concentration in patients who developed leukopenia was significantly higher than that in patients who did not [^bP < 0.01, 474.8 (174.2-1133.6) pmol/8 × 10⁸ red blood cells (RBC) vs 306.0 (62.2-1823.0) pmol/8 × 10⁸ RBC]. In the CT group (n = 65), 6TGN level was also significantly higher in patients who developed leukopenia [^aP < 0.05, 291.7 (80.6-701.5) vs 217.6 (62.9-631.0) pmol/8 × 10⁸ RBC]. 6TGN: 6-thioguanine nucleotide; RBC: Red blood cells.

Figure 3 Receiver operating characteristic curves for the concentration of 6-thioguanine nucleotide with the threshold parameters and nucleoside diphosphate-linked moiety X-type motif 15 R139C genotypes. The area under the receiver operating characteristic curve for the obtained predicted probabilities based on nucleotide concentrations in different nucleoside diphosphate-linked moiety X-type motif 15 R139C genotypes and the level of 6-thioguanine nucleotide was 0.79 (95%CI: 0.76-0.92). 6TGN: 6-thioguanine nucleotide; NUDT15: Nucleoside diphosphate-linked moiety X-type motif 15.