Evidence map›Paper›PMID 41654962›Full record

ArticleBMC pharmacology & toxicology2026

Association between genetically predicted expression of TPMT and azathioprine adverse events.

Alyssa Steitz, Laura L Daniel, Puran Nepal, Alyson L Dickson, Jacy Zanussi, Tyne W Miller-Fleming, Peter S Straub, Wei-Qi Wei, Ge Liu, Jennifer Maizel and 5 more

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Article in BMC pharmacology & toxicology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

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No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Alyssa Steitz *Department of Medicine, Vanderbilt University Medical Center, Nashville, USA.
Laura L Daniel *Department of Medicine, Vanderbilt University Medical Center, Nashville, USA.
Puran NepalDepartment of Medicine, Vanderbilt University Medical Center, Nashville, USA.
Alyson L DicksonDepartment of Medicine, Vanderbilt University Medical Center, Nashville, USA.
Jacy ZanussiDepartment of Medicine, Vanderbilt University Medical Center, Nashville, USA.
Tyne W Miller-FlemingDepartment of Medicine, Vanderbilt University Medical Center, Nashville, USA.
Peter S StraubDepartment of Medicine, Vanderbilt University Medical Center, Nashville, USA.
Wei-Qi WeiDepartment of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, USA.
Ge LiuDepartment of Medicine, Vanderbilt University Medical Center, Nashville, USA.
Jennifer MaizelDepartment of Medicine, University of Miami, Miami, USA.
Nancy J CoxDepartment of Medicine, Vanderbilt University Medical Center, Nashville, USA.
Adriana M HungDepartment of Medicine, Vanderbilt University Medical Center, Nashville, USA.
QiPing FengDepartment of Medicine, Vanderbilt University Medical Center, Nashville, USA.
C Michael SteinDepartment of Medicine, Vanderbilt University Medical Center, Nashville, USA.
Cecilia P ChungDepartment of Medicine, Vanderbilt University Medical Center, Nashville, USA. cecilia.chung@med.miami.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPolymorphisms thiopurine-S-methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15) can increase the risk of azathioprine myelotoxicity, but little is known about other genetic factors that increase risk for azathioprine-associated side effects. PrediXcan is a gene-based association method that estimates the expression of individuals’ genes and examines their correlation to specified phenotypes. To interrogate the utility of using PrediXcan as a tool for detecting associations between genetic factors and azathioprine side effects, we aimed to determine whether the genetically predicted expression of TPMT or NUDT15 was associated with leukopenia or other known side effects of azathioprine.

methodsThis is a retrospective cohort study of 1,364 new users of azathioprine (patients taking azathioprine with an organ transplant indication were excluded) with electronic health record (EHR)-reported White race. We used PrediXcan to impute expression in liver tissue, tested its association with pre-specified phecodes representing known side effects (e.g. skin cancer), and completed chart review to confirm cases.

resultsAmong confirmed cases, patients in the lowest tertile of TPMT predicted expression had significantly higher odds of developing leukopenia (OR = 3.30, 95%CI: 1.07–10.20, p = 0.04) versus those in the highest tertile; no other side effects were significant.

conclusionThe results suggest that this methodology could be deployed on a larger scale to uncover associations between genetic factors and drug side effects for more personalized care.

Indexed as

AzathioprineImmunosuppressive AgentsLeukopeniaMethyltransferasesPyrophosphatasesAdultFemaleHumansMaleMiddle AgedNudix HydrolasesRetrospective StudiesAzathioprineImmunosuppressive AgentsMethyltransferasesNudix HydrolasesNUDT15 protein, humanPyrophosphatasesthiopurine methyltransferaseTPMT protein, humanAzathioprineLeukopeniaPersonalized medicinePharmacogeneticsPharmacogenomicsPrediXcan

Identifiers

PMID41654962
PMCPMC13295855

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