The full content of Annals is available to subscribers

Subscribe/Learn More  >
Brief Communications |

Thiopurine Methyltransferase Genotype Predicts Therapy-Limiting Severe Toxicity from Azathioprine

Alison J. Black, MB, ChB; Howard L. McLeod, PharmD; Hillary A. Capell, MB, ChB, MD, FRCP; Robert H. Powrie, BSc; Lloyd K. Matowe, MSc; Stuart C. Pritchard, MSc; Elaina S.R. Collie-Duguid, PhD; and David M. Reid, MB, ChB, MD, FRCP
[+] Article, Author, and Disclosure Information

From the University of Aberdeen and Aberdeen Royal Hospitals Trust and Glasgow Royal Infirmary, Glasgow, United Kingdom. Acknowledgments: The authors thank research nurse Rosemary Hampson. Grant Support: In part by the Wellcome Trust (046607) and the Beit Trust. Dr. Reid is also supported by the Arthritis Research Campaign. Requests for Reprints: Howard L. McLeod, PharmD, Department of Medicine & Therapeutics, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, United Kingdom; e-mail, h.l.mcleod@abdn.ac.uk. Current Author Addresses: Dr. Black: The Osteoporosis Research Unit, Aberdeen Royal Hospitals Trust, Aberdeen AB25 2ZD, United Kingdom.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1998;129(9):716-718. doi:10.7326/0003-4819-129-9-199811010-00007
Text Size: A A A

Background: Substantial hematologic toxicity limits the use of azathioprine.

Objective: To evaluate 1) polymorphic inactivation of azathioprine by thiopurine methyltransferase and 2) clinical toxicity.

Design: Prospective cohort study.

Setting: Two rheumatology units.

Patients: 67 patients for whom azathioprine was prescribed as second-line therapy for rheumatic disease.

Measurements: Polymerase chain reaction-based assays were used to detect mutations in thiopurine methyltransferase. The primary end point was discontinuation of azathioprine therapy because of toxicity.

Results: Six of 67 patients (9%) were heterozygous for mutant thiopurine methyltransferase alleles. Five of the 6 patients discontinued therapy within 1 month of starting treatment because of low leukocyte counts. The sixth patient did not adhere to treatment. Patients with wild-type thiopurine methyltransferase alleles received therapy longer than did patients with mutant alleles (median duration of therapy, 39 weeks [range, 6 to 180 weeks] and 2 weeks [range, 2 to 4 weeks], respectively; P = 0.018).

Conclusion: Analysis of thiopurine methyltransferase genotype is a quick way to identify patients at risk for acute toxicity from azathioprine.


Grahic Jump Location
Figure 1.
Influence of thiopurine methyltransferase genotype on the duration of azathioprine therapy (61 patients had the wild-type TPM allele and 5 patients had the mutant TPM allele).
Grahic Jump Location




Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).


Submit a Comment/Letter
Submit a Comment/Letter

Summary for Patients

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.


Buy Now for $32.00

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Related Articles
Topic Collections
PubMed Articles
Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.