Toxicity of azathioprine: why and when? analysis of the prevalence of polymorphism in Joinville, SC, Brazil

Abstract

CONTEXT: The use of thiopurine drugs such as azathioprine and 6-mercaptopurine has become quite common in the treatment of inflammatory bowel disease, transplantation and acute leukemias. Despite their effectiveness, these drugs are capable of causing drug-induced toxicity with the risk of death by myelosuppression. It is now known that these complications occur because of genetic polymorphisms of the thiopurinemethyltransferase (TPMT) enzyme, responsible for its metabolism. OBJECTIVE: To assess the prevalence of thiopurine methyltransferase polymorphisms in the population of Joinville, SC, Brazil. METHODS: We analyzed the frequency of four main allelic variants of the TPMT gene in 199 blood donors from Joinville, from February to April 2010. RESULTS: The normal allele ("wild-type") was found in 93.9% of subjects studied. TPMT variants were detected in 12 subjects (6.03%). CONCLUSIONS: From this study, it was estimated at 6% the risk of toxicity by the administration of azathioprine and 6-mercaptopurine to patients in Joinville.