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      Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing.

      Clinical Pharmacology and Therapeutics

      6-Mercaptopurine, administration & dosage, adverse effects, metabolism, Antimetabolites, Antineoplastic, Azathioprine, Dose-Response Relationship, Drug, Genotype, Humans, Immunosuppressive Agents, Methyltransferases, genetics, Thioguanine

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          Abstract

          Thiopurine methyltransferase (TPMT) activity exhibits monogenic co-dominant inheritance, with ethnic differences in the frequency of occurrence of variant alleles. With conventional thiopurine doses, homozygous TPMT-deficient patients (~1 in 178 to 1 in 3,736 individuals with two nonfunctional TPMT alleles) experience severe myelosuppression, 30-60% of individuals who are heterozygotes (~3-14% of the population) show moderate toxicity, and homozygous wild-type individuals (~86-97% of the population) show lower active thioguanine nucleolides and less myelosuppression. We provide dosing recommendations (updates at http://www.pharmgkb.org) for azathioprine, mercaptopurine (MP), and thioguanine based on TPMT genotype.

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          Author and article information

          Journal
          21270794
          3098761
          10.1038/clpt.2010.320

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