Thiopurine S-methyltransferase (TPMT) genotype does not predict adverse drug reactions to thiopurine drugs in patients with inflammatory bowel disease

Background: Azathioprine and mercaptopurine (MP) are well established treatments for inflammatory bowel disease but they have severe adverse effects that prevent their use in some patients. The likelihood and type of adverse effect may relate to thiopurine methyltransferase (TPMT) enzyme activity and genotype. Aim: To compare the TPMT genotype frequencies in patients with inflammatory bowel disease who have had severe adverse effects to those who tolerate azathioprine or MP (controls). Methods: Patients with inflammatory bowel disease who had been treated with azathioprine or MP in Christchurch between 1996 and 2002 were identified. Patients with adverse effects, and controls, were invited to provide a peripheral blood sample for analysis of TPMT genotype. The genotype frequencies were then compared between the two groups. Results: Fifty-six patients were identified with adverse effects requiring cessation of therapy, of which 50 were genotyped. Reactions included allergic-type (25%), hepatitis (33%), nausea/vomiting (14%), bone marrow suppression (10%), pancreatitis (6%) and other (12%). Five of 50 patients with reactions had TPMT genotype *1/*3, one had *3/*3, and the rest had the wildtype genotype *1/*1. The patient with genotype *3/*3 had severe pancytopenia requiring hospitalization. Three of 50 controls had the *1/*3 genotype and the rest were *1/*1. Conclusions: The TPMT allele frequency in our population with inflammatory bowel disease is similar to that reported elsewhere. There was a slight trend for more frequent TPMT mutations in the patients with adverse reactions, but this was not statistically significant. Most patients with reactions did not have gene mutations.