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

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

Category	Leukopenia		% of total	OR (95%CI)	P value
	Yes	No
NUDT15 R139C TT	4	0	4/4 (100%)	↑↑↑	-
NUDT15 R139C CT + 6TGN > 319.2	14	1	14/15 (93.3%)	225.0 (27.6-1836.2)	1.5 × 10-14
NUDT15 R139C CT + 6TGN < 319.2	19	31	19/50 (38.0%)	9.9 (4.5-21.6)	8.1 × 10-11
NUDT15 R139C CC + 6TGN > 411.5	21	82	21/103 (20.4%)	4.1 (2.0-8.5)	4.8 × 10-5
NUDT15 R139C CC + 6TGN < 411.5	14	225	14/239 (5.9%)	Reference	-
Total	72	339	72/411 (17.5%)

Patients carrying the TT allele, irrespective of the concentration of 6-thioguanine nucleotide (6TGN), were at the highest risk, as all of them developed leukopenia in this study. Patients with the CT genotype and a 6TGN concentration above the cut-off value of 319.2 pmol/8 × 10⁸ red blood cells (RBC) were at the second highest risk of developing leukopenia [OR 225.0 (95%CI: 27.6-1836.2)], followed by those carrying the CT genotype with a 6TGN concentration below 319.2 pmol/8 × 10⁸ RBC [OR = 9.9 (95%CI: 4.5-21.6)] and those carrying the CC genotype with a 6TGN concentration above 411.5 pmol/8 × 10⁸ RBC [OR 4.1 (95%CI: 2.0-8.5)]. NUDT15: Nucleoside diphosphate-linked moiety X-type motif 15; 6TGN: 6-thioguanine nucleotide.