Nudix Hydroxylase 15 Mutations Strongly Predict Thiopurine-Induced Leukopenia Across Different Asian Ethnicities: Implications for Screening in a Diverse Population
Background and Aims Thiopurines, which are immunosuppressive drugs for maintaining remission for inflammatory bowel disease, are known to cause myelotoxicity in patients with Nudix Hydroxylase 15 ( NUDT15 ) genetic variants in some Asian countries with monoethnic populations. We aimed to investigate...
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Published in | Frontiers in medicine Vol. 9; p. 880937 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Frontiers Media S.A
05.08.2022
|
Subjects | |
Online Access | Get full text |
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Summary: | Background and Aims
Thiopurines, which are immunosuppressive drugs for maintaining remission for inflammatory bowel disease, are known to cause myelotoxicity in patients with Nudix Hydroxylase 15 (
NUDT15
) genetic variants in some Asian countries with monoethnic populations. We aimed to investigate the association of
NUDT15
variants with leukopenia in a multiethnic population in Southeast Asia.
Methods
Patients with a confirmed diagnosis of inflammatory bowel disease were recruited. We collected demographic and clinical characteristics and whole blood counts before and after initiating thiopurines. Thiopurine S-methyltransferase (
TPMT
) and
NUDT15
genotypes were analyzed with the single nucleotide polymorphisms (SNPs) genotyping assay. Leukopenia was defined as a white blood cell (WBC) count < 3,000/μl.
Results
In this study, 19 (18.6%) of the 102 patients who had adequate thiopurine therapy experienced leukopenia, 11 patients (57.9%) had
NUDT15
c.415C > T variants, 2 patients (10.5%) had
NUDT15
c.52G > A variants while one (5.3%) had a
TPMT
variation. Individually,
NUDT15
c.415C > T had a sensitivity and specificity of 57.9% and 94.0% (odds ratio [
OR
] = 21.45, 95%
CI
5.94–77.41,
p
< 0.001), respectively, for predicting thiopurine-induced leukopenia, while
NUDT15
c.52G > A was only observed in patients with leukopenia. As compared with patients with wild-type
NUDT15
, both
NUDT15
variations had a combined sensitivity and specificity of 68.4% and 94%, respectively (
OR
= 33.80, 95%
CI
8.99–127.05,
p
< 0.001), for predicting thiopurine-induced leukopenia as well as a shorter onset to leukopenia (median onset [months] 2.0 vs. 5.5;
p
= 0.045). Sub-group analysis showed that both
NUDT15
variations were strongly associated with leukopenia among the Chinese and Indians but not among the Malays.
Conclusion
Nudix Hydroxylase 15
variants strongly predicted thiopurine-induced leukopenia across a multiethnic Southeast Asian population, particularly among the Chinese and Indians. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Mitsuhiro Takeno, Nippon Medical School Musashi Kosugi Hospital, Japan This article was submitted to Gastroenterology, a section of the journal Frontiers in Medicine Reviewed by: Masaaki Mori, Tokyo Medical and Dental University, Japan; Prateek Bhatia, Postgraduate Institute of Medical Education and Research, India |
ISSN: | 2296-858X 2296-858X |
DOI: | 10.3389/fmed.2022.880937 |