Distribution of ITPA P32T alleles in multiple world populations

Abstract

Dose-limiting toxicity from azathioprine treatment affects up to 37% of patients. Screening for thiopurine methyltransferase (TPMT) polymorphisms will prospectively identify approximately 10% of patients. Recently, a polymorphism in the inosine triphosphate pyrophosphatase gene (ITPA) has been associated with severe azathioprine toxicity. We demonstrate here that this proline to threonine substitution at codon 32 in the ITPA gene is found at low frequency in Central/South American populations (1-2%), at a constant frequency across Caucasian and African populations (6-7%), and is highest in Asian populations (14-19%). This data is consistent with previously described allele frequencies in other Caucasian (7%), African (5%), and Asian (11-15%) populations. This data provides a foundation on which prospective screening studies can be planned to identify patients at risk for severe toxicity from azathioprine therapy. © The Japan Society of Human Genetics and Springer-Verlag 2004.