The thiopurine drugs azathioprine (AZA) and 6-mercaptopurine (6-MP) are effective for the treatment of inflammatory bowel disease (IBD) and their prescription is increasing. Haematotoxicity, which can lead to potentially life threatening bone marrow suppression, represents the most serious side effect of thiopurine therapy. It has been attributed to the accumulation of active cytotoxic metabolites of AZA/6-MP, collectively called 6-thioguanine nucleotides, resulting from a deficiency in thiopurine catabolism specifically catalysed by the thiopurine S-methyltransferase (TPMT) enzyme. Genotyping tests are now available to identify deficient and intermediate methylators who are, respectively, homozygous and heterozygous for non-functional alleles of the TPMT gene. As pointed out by Lennard in the leading article (Gut 2002;51:143–6), it is clear that myelosuppression may be caused by other factors in addition to variable TPMT.

Since the identification of the molecular …