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From pharmacogenetics to pharmacometabolomics: SAM modulates TPMT activity
Karas Kuželički, Nataša ...
Aim: In the present study, the influence of SAM on TPMT activity in vivo on human subjects was investigated. Subjects & 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, aset 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 Ž 10-13) and SAM levels (p = 1 Ž 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. Conclusion: SAM represents a potential pharmacometabolomic marker and therapeutic agent in TPMT-heterozygous subjects.
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