The prevalence and impacts of NUDT15 variants in pediatric-onset inflammatory bowel disease patients in Taiwan.

NUDT15

NUDT15 intermediate and poor metabolizer phenotypes associated with thiopurine-induced neutropenia

This study assessed the prevalence and impact of NUDT15 variants in 73 patients with pediatric-onset inflammatory bowel disease followed at National Taiwan University Hospital from 2023 to 2025. Based on NUDT15 genotype, 58 patients (79.45%) were normal metabolizers, 12 (16.44%) intermediate and 3 (4.11%) poor metabolizers. Among the 48 thiopurine users, 9 (18.75%) developed neutropenia and 3 (6.25%) severe neutropenia, including two poor metabolizers; intermediate and poor metabolizer phenotypes were significantly associated with neutropenia (OR 13.39, 95% CI 2.50-71.64, p = 0.002). The NUDT15*3 and NUDT15*6 alleles were more frequent in this cohort than in the East Asian group, and the proportion of poor metabolizers was higher than in other East Asian areas. The authors recommend considering preemptive NUDT15 genotyping, including NUDT15*3 and NUDT15*6, in pediatric-onset inflammatory bowel disease.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The association is strong but very imprecise (CI 2.50 to 71.64), based on 48 exposed patients and 9 events: the study confirms the role of NUDT15 in children more than it quantifies it. The useful point is the emphasis on NUDT15*6, a reminder that genotyping restricted to a few common alleles can miss poor metabolizers depending on patient ancestry — one more argument for reading the whole gene, already captured by an exome or a genome.

Analysis by Dr Thibaut Benquey