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

Background

Thiopurines are important therapeutic agents for patients with inflammatory bowel disease (IBD), and the Nudix hydrolase 15 (NUDT15) gene has been reported to be associated with the safety of thiopurine use. We investigated the prevalence of NUDT15 variants and their impacts in the pediatric-onset IBD group in Taiwan.

Methods

Seventy-three pediatric-onset IBD patients followed up at National Taiwan University Hospital from 2023 to 2025 were recruited. Every patient had NUDT15 genotyping and was classified as one of three phenotypes: the normal, intermediate, and poor metabolizers. The association of NUDT15 genotypes, phenotypes, thiopurine dosage, and absolute neutrophil count (ANC) was analyzed.

Results

According to NUDT15 genotypes, 58 patients (79.45%) were normal metabolizers, 12 (16.44%) were intermediate metabolizers, and 3 (4.11%) were poor metabolizers in this cohort. Neutropenia occurred in 9 of 48 patients (18.75%) who had thiopurine use. Three thiopurine users (6.25%) developed severe neutropenia, including two poor metabolizers. The intermediate and poor metabolizers are significantly associated with neutropenia in thiopurine users (OR = 13.39, 95% CI = 2.50-71.64, p = 0.002). The mutant allele NUDT15*3 and NUDT15*6 had a higher frequency in our cohort than the East Asian group.

Conclusion

The NUDT15 variants are significantly associated with neutropenia in thiopurine users. The prevalence of poor metabolizers is higher in our study group compared to other East Asian areas, and the distribution of NUDT15 genotypes is different. Preemptive NUDT15 genotyping, including NUDT15*3 and NUDT15*6, should be considered in the pediatric-onset IBD group.