title: Thiopurine S-methyltransferase pharmacogenetics: genotype to phenotype correlation in the Slovenian population.
abstract: The toxicity of thiopurine drugs has been correlated to the activity of thiopurine S-methyltransferase (TPMT), whose interindividual variation is a consequence of genetic polymorphisms. We have herein investigated the relevance of some genetic markers for the prediction of thiopurine-related toxicities and to determine the genotype to phenotype correlation in the Slovenian population. The most prevalent mutant allele in the Slovenian population is TPMT*3A (4.1%), followed by TPMT*3C (0.5) and TPMT*3B (0.3), while the TPMT*2 allele was not found in any of the examined samples. TPMT enzyme activity distribution in the subgroup sample was bimodal and as such correlated with genetic data. Using a cutoff value of 9.82 pmol/10(7) RBC per h, the genetic data correctly predicted TPMT enzyme activity in 91.6% of the examined individuals. Pharmacogenetic TPMT analyses have therefore proved to have significant clinical implications for prediction of individuals' responses to treatment with thiopurine drugs in order to avoid possible life-threatening therapy-related toxicities.
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: M
authors.initials: M
authors.lastname: Milek
authors.forename: J
authors.initials: J
authors.lastname: Murn
authors.forename: Z
authors.initials: Z
authors.lastname: Jaksic
authors.forename: J
authors.initials: J
authors.lastname: Lukac Bajalo
authors.forename: J
authors.initials: J
authors.lastname: Jazbec
authors.forename: I
authors.initials: I
authors.lastname: Mlinaric Rascan
mesh_terms: D004247:DNA / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism*; D010597:Pharmacogenetics; D010641:Phenotype; D011687:Purines / Q000378:metabolism; D017524:Slovenia
chemical_list: D011687:Purines; D004247:DNA; D008780:Methyltransferases; C022745:thiopurine methyltransferase