The DOI matches its Crossref record.
Pharmacogenetics of acute azathioprine toxicity: Relationship to thiopurine methyltransferase genetic polymorphism
Abstract
Azathioprine therapy can cause acute myelosuppression. Toxicity is in part caused by the incorporation of azathioprine-derived 6-thioguanine nucleotides (6-TGN) into deoxyribonucleic acid (DNA). The enzyme thiopurine methyltransferase (TPMT) plays an important role in azathioprine catabolism. TPMT activity is controlled by a common genetic polymorphism, and one in 300 subjects has very low enzyme activity. Azathioprine was withdrawn in five study patients because of acute myelosuppression. The duration of azathioprine treatment was 21 to 70 days (median, 28), and the daily oral dose was 1.0 to 2.5 mg/kg. Sixteen control patients who had been taking oral azathioprine (1.1 to 2.0 mg/kg daily for more than 6 months) with no history of myelosuppression were studied. All subjects had normal liver and kidney function. When compared with the control group, the five patients with myelosuppression had very low TPMT activities and abnormally high 6-TGN concentrations. Inherited low TPMT activity appears to be a major risk factor for acute azathioprine-induced myelosuppression.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cited by
Diagnosis and management of autoimmune hepatitis
Manns, M. P., Czaja, A. J., Gorham, J. D., Krawitt, E. L., Mieli-Vergani, G., Vergani, D., & Vierling, J. M. (2010) · Hepatology · doi:10.1002/hep.23584 · Cited by 1,442
Karran, P., & Attard, N. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2292 · Cited by 477
Azathioprine for Long-Term Maintenance of Remission in Autoimmune Hepatitis
Johnson, P. J., McFarlane, I. G., & Williams, R. (1995) · New England Journal of Medicine · doi:10.1056/nejm199510123331502 · Cited by 382
Pharmacogenomics: Unlocking the Human Genome for Better Drug Therapy
McLeod, H. L., & Evans, W. E. (2001) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.41.1.101 · Cited by 331
Marinaki, A. M., Ansari, A., Duley, J. A., Arenas, M., Sumi, S., Lewis, C. M., Shobowale-Bakre, E.-M., Escuredo, E., Fairbanks, L. D., & Sanderson, J. D. (2004) · Pharmacogenetics · doi:10.1097/00008571-200403000-00006 · Cited by 323
Metadata
- Authors
- Lennard, L., Van Loon, J. A., & Weinshilboum, R. M.
- Venue
- Clinical Pharmacology and Therapeutics
- Publisher
- Wiley
- Published
- 1989-08
- Volume
- 46
- Issue
- 2
- Pages
- 149-154
- ISSN
- 0009-9236 (ISSN-L)
- 1532-6535
- OpenAlex
- W2029841402
- Cited by
- 593
- References
- 0
- FWCI
- 5.85
- Type
- journal article
- Language
- en
- Open access
- closed
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Pharmacogenetics of acute azathioprine toxicity: Relationship to thiopurine methyltransferase genetic polymorphism. https://app.cochat.ai/papers/10.1038/clpt.1989.119
- The paper
- Lennard, L., Van Loon, J. A., & Weinshilboum, R. M. (1989). Pharmacogenetics of acute azathioprine toxicity: Relationship to thiopurine methyltransferase genetic polymorphism. Clinical Pharmacology and Therapeutics. https://doi.org/10.1038/clpt.1989.119
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
