title: From pharmacogenetics to pharmacometabolomics: SAM modulates TPMT activity.
abstract: OBJECTIVE
  In the present study, the influence of SAM on TPMT activity in vivo on human subjects was investigated.
  
  
  METHODS
  A total of 1017 donors from the Estonian Genome Center of the University of Tartu (Estonia) were genotyped for common TPMT variants, evaluated for TPMT activity, SAM levels, a set of 19 biochemical and ten hematological parameters and demographic data.
  
  
  RESULTS
  After adjustment in multiple regression models and correction for multiple testing, from the 43 factors that were tested, only TPMT genotype (p = 1 × 10(-13)) and SAM levels (p = 1 × 10(-13)) were found to significantly influence TPMT activity. The influence of SAM on TPMT activity was more pronounced in TPMT-heterozygous than wild-type individuals.
  
  
  CONCLUSIONS
  SAM represents a potential pharmacometabolomic marker and therapeutic agent in TPMT-heterozygous subjects.
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia.
authors.forename: Nataša
authors.initials: N
authors.lastname: Karas-Kuželički
authors.forename: Alenka
authors.initials: A
authors.lastname: Šmid
authors.forename: Riin
authors.initials: R
authors.lastname: Tamm
authors.forename: Andres
authors.initials: A
authors.lastname: Metspalu
authors.forename: Irena
authors.initials: I
authors.lastname: Mlinarič-Raščan
mesh_terms: D000328:Adult; D004957:Estonia; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D010597:Pharmacogenetics / Q000379:methods; D012436:S-Adenosylmethionine / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D012436:S-Adenosylmethionine; D008780:Methyltransferases; C022745:thiopurine methyltransferase
keywords: 6-mercaptopurine; ALL; S-adenosyl methionine; pharmacogenetics; thiopurine-S-methyltransferase