Aplasia after azathioprine administration: role of the thiopurine methyltransferase genetic polymorphism

BACKGROUND: Azathioprine is an immunosuppressor drug widely used in the tre atment of autoimmune diseases. Adverse effects during treatment are related to the activity of thiopurine methyltransferase (TPMT), an enzyme which pl ays a role in azathioprine metabolism. The presence of the allelic variants of the TPMT gene allows us to classify patients into three different group s: high, moderate and low risk of myelosuppression after receiving standard doses of azathioprine. PATIENTS AND METHODS: Study of the allelic variants of the TPMT gene in the positions 460 and 719 with PCR methods in a patient with Crohn's disease, who developed aplasia after receiving azathioprine. The study was extended to his relatives. RESULTS: The patient under study carried the most frequent variant allele o f the TPMT gene associated with low enzymatic activity. The mother and one sister of the patient were also carriers of this allelic variant. CONCLUSIONS: Genotyping the allelic variants of the TPMT gene is a useful m ethod to identify patients at moderate or high risk of myelosuppression aft er administration of azathioprine.