Prevalence and impact of Thiopurine S-methyltransferase (TPMT) and Nudix hydrolase 15 (NUDT15) polymorphisms on the occurrence of myelosuppression in Thai patients with inflammatory bowel disease receiving thiopurine therapy.
- 1Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Abstract
Introduction
Thiopurine-induced myelosuppression (TIM) is an important side effect influenced by 2 main genetic polymorphisms, thiopurine-S-methyltransferase (TPMT) and NUDT15. The data on Southeast Asian inflammatory bowel disease (IBD) patients remain limited. Our study aimed to determine the relationship between TPMT and NUDT15 polymorphisms and TIM following thiopurine treatment in Thai patients with IBD.Methods
We performed a retrospective cohort study of IBD patients receiving azathioprine with active follow-up at the IBD clinic. TPMT and NUDT15 polymorphisms were checked. Medical records were reviewed for TIM occurrence and its genetic associations.Results
A total of 124 IBD patients (73 Crohn's disease, 51 ulcerative colitis; mean age 46.9 years) were included. Initial azathioprine dosing was 0.87 mg/kg/day, titrated to 1.54 mg/kg/day. TPMT variants were found in 6 patients (4.8%; 5 heterozygous and 1 homozygous) and NUDT15 variants in 21 patients (16.9%; 20 heterozygous and 1 homozygous). Over a 7.6-year follow-up, TIM occurred in 12 patients (9.7%). TIM rate was not significantly different among TPMT polymorphisms (wild-type 9.3%, heterozygous 20%, homozygous 0%), but was significantly different among NUDT15 polymorphisms (7.8% wild-type and heterozygous/homozygous 19%). The cumulative rates of TIM at 6, 12, and 60 months were 2.1%, 3.2%, and 7.2% in wild type and 0%, 5%, and 10% in NUDT15 heterozygous mutation. The only participant with a homozygous mutation developed TIM within the first month.Conclusion
NUDT15 polymorphisms are more common than TPMT variants in this study and are significantly associated with TIM. Pre-treatment genotyping may be considered, taking into account local mutation prevalence, test availability, and cost-effectiveness.
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BibTeX
@article{phoojaroenchanachai2026prevalence,
title = {{Prevalence and impact of Thiopurine S-methyltransferase (TPMT) and Nudix hydrolase 15 (NUDT15) polymorphisms on the occurrence of myelosuppression in Thai patients with inflammatory bowel disease receiving thiopurine therapy.}},
author = {Rujirada Phoojaroenchanachai and Thanaboon Chaemsupaphan and Onuma Sattayalertyanyong and Nichcha Subdee and Phutthaphorn Phaophu and Marianee Salaemae and Julajak Limsrivilai},
journal = {Crohn's \& colitis 360},
year = {2026},
month = oct,
doi = {10.1093/crocol/otag115},
url = {https://europepmc.org/article/MED/42927292},
note = {CC BY},
}
RIS
TY - JOUR
TI - Prevalence and impact of Thiopurine S-methyltransferase (TPMT) and Nudix hydrolase 15 (NUDT15) polymorphisms on the occurrence of myelosuppression in Thai patients with inflammatory bowel disease receiving thiopurine therapy.
AU - Rujirada Phoojaroenchanachai
AU - Thanaboon Chaemsupaphan
AU - Onuma Sattayalertyanyong
AU - Nichcha Subdee
AU - Phutthaphorn Phaophu
AU - Marianee Salaemae
AU - Julajak Limsrivilai
PY - 2026
DA - 2026/10/09
JO - Crohn's & colitis 360
DO - 10.1093/crocol/otag115
UR - https://europepmc.org/article/MED/42927292
AB - Introduction Thiopurine-induced myelosuppression (TIM) is an important side effect influenced by 2 main genetic polymorphisms, thiopurine-S-methyltransferase (TPMT) and NUDT15. The data on Southeast Asian inflammatory bowel disease (IBD) patients remain limited. Our study aimed to determine the relationship between TPMT and NUDT15 polymorphisms and TIM following thiopurine treatment in Thai patients with IBD.Methods We performed a retrospective cohort study of IBD patients receiving azathioprine with active follow-up at the IBD clinic. TPMT and NUDT15 polymorphisms were checked. Medical records were reviewed for TIM occurrence and its genetic associations.Results A total of 124 IBD patients (73 Crohn's disease, 51 ulcerative colitis; mean age 46.9 years) were included. Initial azathioprine dosing was 0.87 mg/kg/day, titrated to 1.54 mg/kg/day. TPMT variants were found in 6 patients (4.8%; 5 heterozygous and 1 homozygous) and NUDT15 variants in 21 patients (16.9%; 20 heterozygous and 1 homozygous). Over a 7.6-year follow-up, TIM occurred in 12 patients (9.7%). TIM rate was not significantly different among TPMT polymorphisms (wild-type 9.3%, heterozygous 20%, homozygous 0%), but was significantly different among NUDT15 polymorphisms (7.8% wild-type and heterozygous/homozygous 19%). The cumulative rates of TIM at 6, 12, and 60 months were 2.1%, 3.2%, and 7.2% in wild type and 0%, 5%, and 10% in NUDT15 heterozygous mutation. The only participant with a homozygous mutation developed TIM within the first month.Conclusion NUDT15 polymorphisms are more common than TPMT variants in this study and are significantly associated with TIM. Pre-treatment genotyping may be considered, taking into account local mutation prevalence, test availability, and cost-effectiveness.
SN - 2631-827X
ER -