Thiopurine methyltransferase (TPMT) pharmacogenetics: Polymorphism characterization

D. Otterness, C. Szumlanski, T. Wood, L. Lennard, B. Klemetsdal, J. Aarbakke, J. Park-Hah, H. Iven, E. Branum, J. O'Brien, R. Weinshilboum

Research output: Contribution to journalArticlepeer-review


The TPMT genetic polymorphism is responsible for large individual differences in thiopurine therapeutic efficacy and toxicity. The "wild type" allele, TPMT*1, and three variant low activity alleles have been described previously. Allele *2 has a G238C mutation (Ala80Pro). The most common low activity variant allele in Caucasians, *3A, has G460A and A719G transitions (Ala154Thr and Tyr240Cys); while the variant allele, *4, contains a G to A transition at the intron 9-exon 10 splice junction. In the present study, 4 of 6 "intermediate activity" Norwegian samples were heterozygous for *1/*3A, while 2 were heterozygous at nucleotide 719 only (*7/*3C). Four of 10 Korean samples with "lower" TPMT activity were also heterozygous, * 1/*3C. We also genotyped 27 "intermediate" activity clinical samples from Mayo. The most common variant allele, *3A, had a frequency of 58%, and 5 other variant alleles were identified. Ten of 16 "very low" TPMT samples were homozygous for *3A. DNA-based tests for TPMT might prove clinically useful in some situations.

Original languageEnglish (US)
Pages (from-to)165
Number of pages1
JournalClinical pharmacology and therapeutics
Issue number2
StatePublished - 1997

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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