Premium
Detection of one single mutation predicts thiopurine S‐methyltransferase activity in a population of Saami in northern Norway
Author(s) -
Loennechen Thrina,
Utsi Egil,
Hartz Ingeborg,
Lysaa Roy,
Kildalsen Hanne,
Aarbakke Jarle
Publication year - 2001
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1067/mcp.2001.117445
Subject(s) - thiopurine methyltransferase , genotyping , allele , population , genetics , allele frequency , biology , genotype , medicine , azathioprine , gene , disease , environmental health
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. Clinical Pharmacology & Therapeutics (2001) 70 , 183–188; doi: 10.1067/mcp.2001.117445