Correlation of thiopurine methyltransferase and inosine triphosphate pyrophosphatase polymorphisms and adverse effects induced by azathioprine treatment in Taiwanese dermatology patients

Abstract

Background: Azathioprine is used as an immunosuppressant and corticosteroid-sparing agent for the treatment of several cutaneous diseases. The mutation of thiopurine methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) has been reported to result in the accumulation of toxic thiopurine metabolites and to increase the adverse effects during azathioprine treatment. In the Chinese population, TPMT∗3C and ITPA C94A polymorphisms have been documented. Methods: Genotyping was performed for TPMT and ITPA polymorphisms in 92 unrelated healthy volunteers and in 74 dermatology patients (46 with adverse effects and 28 without adverse effects) during azathioprine treatment. Results: Two functional polymorphisms, TPMT∗3C and ITPA C94A, were detected. After analysis, ITPA C94A showed weak association with nausea/vomiting induced by azathioprine. Furthermore, we revealed that the ITPA 94 A allele was most common in patients with nausea/vomiting and developing slow-appearing adverse effects (67%), followed by patients with nausea/vomiting but not developing slow-appearing adverse effects (50%) and patients without nausea/vomiting but developing slow-appearing adverse effects (25%). Conclusion: Adverse reaction to azathioprine cannot be predicted by TPMT polymorphism. However, genetic testing of ITPA polymorphism may be more important for the prediction of nausea/vomiting in Taiwanese. Currently, regular blood tests and clinical vigilance remain most important in preventing severe drug reactions during clinical use of azathioprine.

Keywords

• adverse effects
• azathioprine
• gene polymorphism
• inosine triphosphate pyrophosphatase
• thiopurine methyltransferase