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Pitfalls in the determination of mutant alleles of the thiopurine methyltransferase gene

Leukemia volume 15, pages 1792–1793 (2001)Cite this article

Thiopurine methyltransferase (TPMT) is a methylating enzyme which is involved in the metabolism of thiopurines. The enzyme is known to exhibit an autosomal codominant polymorphism with 89–94% of all individuals studied having a high activity, 6–11% an intermediate activity and 0.3% having a very low or non-detectable activity. The gene encoding TPMT is localized on chromosome 6. Eight variant alleles of the gene are reported to be associated with decreased TPMT enzyme activity, and TPMT*3 mutations are the most prevalent.1,2 Heterozygotes and homozygotes for these alleles are at moderate and high risk, respectively, for thiopurine drug toxicity. In Caucasians and South West Asians, TPMT*3A (transitions G460A and A719G) is the most prevalent mutant allele whereas in a Chinese, a Korean and an African population, as well as an African-American population the TPMT*3C (A719G) mutation is more common. The TPMT*3A allele is believed to have arisen as a result of a TPMT*3B (G460A) mutation on an ancestral TPMT*3C variant allele.1

From reviewing the literature on TPMT populations studies and from our own genotyping, we note that 19 cases of TPMT*3B have been reported from a total of 12208 alleles, a frequency of 0.16%.3,4,5,6,7 The mutations TPMT*3A and TPMT*3C accounted for 4.00% (488 alleles) and 1.38% (168 alleles), respectively, of the total amount of alleles published.

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Authors and Affiliations

  1. Department of Pediatrics 424, UMC St Radboud, Nijmegen, The Netherlands

    C Brouwer, LHJ Lambooy & RA De Abreu

  2. Guy's Hospital Purine Research Unit, London, UK

    AM Marinaki, JA Duley & M Shobowale-Bakre

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  1. C Brouwer
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Brouwer, C., Marinaki, A., Lambooy, L. et al. Pitfalls in the determination of mutant alleles of the thiopurine methyltransferase gene. Leukemia 15, 1792–1793 (2001). https://doi.org/10.1038/sj.leu.2402285

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