Inosine triphosphatase (ITPA; EC 3.6.1.19) catalyzes the hydrolysis of ITP to inosine monophosphate, thereby recycling purines that might otherwise be trapped in the form of ITP (1)(2). Two single-nucleotide polymorphisms associated with ITPA deficiency have been identified in the ITPA gene. Individuals who are homozygous for a 94C>A (P32T) mutation have a total deficiency of enzyme activity and accumulate ITP intracellularly, whereas 94C>A heterozygotes have decreased ITPA activity that is 22.5% of the control mean value (2). A second mutation, IVS2 + 21A>C, was detected in ITPA-deficient families. This intronic mutation has a more subtle effect on ITPA activity, and heterozygotes have activities that are, on average, ∼60% of the control mean. It was presumed that the IVS2 + 21A>C mutation alters the relatively conserved adenine of a putative splicing branch site, leading to abnormal mRNA splicing (2). Although ITPA deficiency is not related to any defined pathology in humans, it was recently demonstrated that polymorphisms in the ITPA gene associated with ITPA deficiency have pharmacogenomic implications for patients treated with thiopurines (3). In a retrospective study involving patients with inflammatory bowel disease receiving azathioprine, Marinaki et al. (3) observed that the 94C>A deficient allele was significantly related to the adverse drug reactions (ADRs) flu-like symptoms, rash, and pancreatitis. The purine analog 6-mercaptopurine and its prodrug azathioprine (AZA) are widely used in the treatment of leukemia and autoimmune disease, and in transplantation. ADRs to these drugs have been related to a genetic deficiency of thiopurine S -methyltransferase (TPMT; EC 2.1.1.67), which is a key enzyme of thiopurine drug catabolism (4). TPMT deficiency leads to life-threatening myelosuppression by accumulation of active thiopurine metabolites (5). Most ADRs to thiopurines, however, cannot be explained by TPMT deficiency. Thiopurines are more frequently discontinued because of non-dose-dependent ADRs (fever, pancreatitis, nausea) than …