Distribution of ITPA P32T alleles in multiple world populations.
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.
Marsh
Sharon
S
Division of Oncology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8069, St Louis, MO, 63110, USA. smarsh@im.wustl.edu.
King
Cristi R
CR
Division of Oncology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8069, St Louis, MO, 63110, USA.
Ahluwalia
Ranjeet
R
Division of Oncology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8069, St Louis, MO, 63110, USA.
McLeod
Howard L
HL
Division of Oncology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8069, St Louis, MO, 63110, USA.
D000483:Alleles; D001379:Azathioprine / Q000009:adverse effects; D001483:Base Sequence; D017931:DNA Primers; D005828:Genetics, Population; D006801:Humans; D008780:Methyltransferases / Q000235:genetics; D011110:Polymorphism, Genetic; D011755:Pyrophosphatases / Q000235:genetics*; D000097630:Inosine Triphosphatase
D001379:Azathioprine; D017931:DNA Primers; D008780:Methyltransferases; D011755:Pyrophosphatases; D000097630:Inosine Triphosphatase; C022745:thiopurine methyltransferase