Do ITPA and TPMT genotypes predict the development of side effects to AZA?
- 1Department of Chemical Pathology, Mater Misericordiae Hospital and School of Microbial and Molecular Medicine, University of Queensland, Brisbane, Australia
- Correspondence to:
Dr J Duley
Chemical Pathology, Mater Health Services, Raymond Terrace, Brisbane 4211, Australia; john.duley{at}mater.org.au
- inosine triphosphate pyrophosphatase
- thiopurine methyltransferase
- azathioprine
- genotyping
- Crohn’s disease
- inflammatory bowel disease
In a retrospective study of patients with inflammatory bowel disease, van Dieren et al recently reported the absence of a correlation between genotypes for both inosine triphosphate pyrophosphatase (ITPA) and thiopurine methyltransferase (TPMT), with any side effects to azathioprine (AZA) (Gut 2005;54:1664). This contrasts with two other studies. A rigorous prospective study, published recently, has demonstrated a significant association between ITPA genotype and early dropout from AZA therapy.1 Our original publication implicated ITPA in a number of adverse effects, which were independent of myelosuppression.2 Another letter has reported non-association of ITPA with myelosuppression3 but thiopurine induced myelosuppression has been well documented over the past 25 years as associated with TPMT, not ITPA, status.4
However, we draw attention to a peculiar feature of the TPMT results of van Dieren et al that one patient—who suffered severe myelosuppression—was reported as TPMT*3B/*3B genotype. We previously published a meta-analysis of the incidence of the TPMT*3B (G460A) mutation,5 discovering that it is rare, and this has been confirmed by a recent large study, making the chance of homozygosity negligible.6 Indeed, our evidence suggested that even the few …
