From Pharmacogenetics to Pharmacometabolomics: SAM Modulates TPMT Activity

descriptionPublicationkeyboard_double_arrow_right Article 01 Aug 2014 English Publisher:Informa UK LimitedJournal:Pharmacogenomics, volume 15, pages 1,437-1,449 (issn: 1462-2416, eissn: 1744-8042,

Copyright policy )Funded by:EC | ePerMed

Authors: Karas-Kuželički, Nataša; Šmid, Alenka; Tamm, Riin; Metspalu, Andres; Mlinarič-Raščan, Irena;

doi: 10.2217/pgs.14.84

pmid: 25303295

From Pharmacogenetics to Pharmacometabolomics: SAM Modulates TPMT Activity

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Abstract

In the present study, the influence of SAM on TPMT activity in vivo on human subjects was investigated.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.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.SAM represents a potential pharmacometabolomic marker and therapeutic agent in TPMT-heterozygous subjects.

Related Organizations

University of Ljubljana
Slovenia
University of Tartu
Estonia
University of Ljubljana, Faculty of Law
Slovenia

Keywords

Adult, Estonia, Male, Heterozygote, S-Adenosylmethionine, Genotype, Genetic Variation, Methyltransferases, White People, Pharmacogenetics, Humans, Female

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