Typing TPMT and ITPase to detect azathioprine toxicity

Monica Arenas; Anthony Marinaki; Azhar Ansari; Jeremy Sanderson

doi:10.2217/17410541.3.1.45

Typing TPMT and ITPase to detect azathioprine toxicity

Per Med. 2006 Feb;3(1):45-59. doi: 10.2217/17410541.3.1.45.

Authors

Monica Arenas^{1

2

3

4}, Anthony Marinaki^{1

2

3

4}, Azhar Ansari^{1

2

3

4}, Jeremy Sanderson^{1

2

3

4}

Affiliations

¹ Purine Research Laboratory, Guy's Hospital, St Thomas' Street, London SE1 9RT, UK. [email protected].
² [email protected].
³ Guy's & St. Thomas' Hospitals, Department of Gastroenterology, 1st Floor College House, St Thomas' Hospital, London SE1 7EH, UK. [email protected].
⁴ [email protected].

PMID: 29783434
DOI: 10.2217/17410541.3.1.45

Abstract

Genetic variation in thiopurine methyltransferase (TPMT) enzyme activity strongly predicts adverse effects in patients treated with the thiopurine drugs, azathioprine and 6-mercaptopurine, and is one of the classic examples of pharmacogenetics in clinical practice. Recently, polymorphic variation in the gene encoding the enzyme inosine triphosphatase (ITPase) has also been associated with risk of thiopurine-related toxicity. This article reviews the evidence for the role of TPMT and ITPase deficiency as predictors of thiopurine toxicity and makes recommendations for clinical and laboratory practice.

Keywords: 6-mercaptopurine; ITPA; ITPase; TPMT; adverse effects; azathioprine; drug toxicity; inflammatory bowel disease; inosine triphosphatase; inosine triphosphate pyrophosphohydrolase; thiopurine; thiopurine methyl transferase.