title: Detection of one single mutation predicts thiopurine S-methyltransferase activity in a population of Saami in northern Norway.
abstract: Thiopurine S-methyltransferase (TPMT) activity exhibits genetic polymorphism. The purpose of this investigation was to identify TPMT mutant alleles in the Saami population as a basis of developing genotyping tests for prediction of TPMT activity. The most predominant allele in Saamis (n = 194) was the TPMT*3C allele (A719G mutation) representing 92% of the mutant alleles, with an estimated allelic frequency of 3.3%. The most frequent allele in Caucasians (n = 66) living in the same geographic area was the TPMT*3A (A719G and G460A mutations) representing 91% of the mutant alleles, with an estimated allelic frequency of 3.4%. A test for one mutation, A719G, may prospectively identify more than 90% of the Saami individuals who require reduction in thiopurine dose to avoid hematopoietic toxicity. In a Norwegian population, comprising both the major Caucasian population and a minor Saami population, the same genotyping tests (eg, tests for the A719G and G460A mutations) may be used.
authors.affiliation: Department of Pharmacology, Institute of Pharmacy, the Karasjok Heart Centre, University of Tromsø, Norway. thrinal@farmasi.uit.no
authors.forename: T
authors.initials: T
authors.lastname: Loennechen
authors.forename: E
authors.initials: E
authors.lastname: Utsi
authors.forename: I
authors.initials: I
authors.lastname: Hartz
authors.forename: R
authors.initials: R
authors.lastname: Lysaa
authors.forename: H
authors.initials: H
authors.lastname: Kildalsen
authors.forename: J
authors.initials: J
authors.lastname: Aarbakke
mesh_terms: D000328:Adult; D000483:Alleles; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D009664:Norway / Q000208:ethnology; D010641:Phenotype; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics*
chemical_list: D008780:Methyltransferases; C022745:thiopurine methyltransferase