Skip to main content
Article thumbnail
Location of Repository

Thiopurine methyltransferase phenotyping and genotyping in clinical practice preferred access arrangement

By Valerie Graham

Abstract

Thiopurine methyltransferase (TPMT) metabolises the widely prescribed thiopurine drugs. The activity of this enzyme varies between individuals and this can influence treatment success. Rapid and accurate assays of TPMT and 6TGN, the active thiopurine metabolites, are increasingly recognised as valuable clinical tools, to guide dosing and treatment. This work examines and develops methods for determining a patient's TPMT status and measuring 6TGN levels, adapting them for analysis using whole blood rather than washed red blood cell preparations. The advantages and limitations of these new assays in practice are investigated, which clearly shows that the more rapid new methods have increased clinical significance and utility. Experimental work and research provides an increased understanding of factors influencing determination and significance of a patient's TPMT status and thiopurine metabolite levels. This includes possible misclassification of TPMT status when expressing results in relation to patient haemoglobin and a longitudinal study of TPMT activity of patients commencing thiopurine therapy which demonstrates no enzyme induction

Topics: R Medicine (General)
Year: 2010
OAI identifier: oai:etheses.bham.ac.uk:738

Suggested articles

Citations

  1. (2003). 6-thioguanine: a new old drug to procure remission in inflammatory bowel disease. doi
  2. (1989). Analysis of 6-mercaptopurine, 6-thioguanine nucleotides, and 6-thiouric acid in biological fluids by highperformance liquid chromatography. doi
  3. (2004). Genetic determinants of the pre- and postazathioprine therapy thiopurine methyltransferase activity phenotype. doi
  4. (2004). Guidelines for prescribing azathioprine in dermatology. doi
  5. (2008). Long term outcome of using allopurinol co-therapy as a strategy for overcoming thiopurine hepatotoxicity in treating inflammatory bowel disease. Aliment Pharmacol Ther, doi
  6. (1992). Pancytopenia related to azathioprine – an enzyme deficiency caused by a common genetic polymorphism.
  7. (2004). Relevance of thiopurine methyl transferase status in rheumatology patients receiving azathioprine. doi
  8. (2000). Screening of thiopurine Smethyltransferase mutations by horizontal conformation-sensitive gel electrophoresis. Hum Mutat, doi
  9. (1986). Thiopurine methyltransferase: structure-activity relationships for benzoic acid inhibitors and thiophenol substrates. doi
  10. (2009). Who is using the TPMT test in the UK? A review of requests sent to a national referral centre Ann Clin Biochem,

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.