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From pharmacogenetics to pharmacometabolomics: SAM modulates TPMT activity
Nataša Karas-Kuželički1, Alenka Šmid, Riin Tamm
1Faculty of Pharmacy, University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia.
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, 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.
Conclusion:
SAM represents a potential pharmacometabolomic marker and therapeutic agent in TPMT-heterozygous subjects.
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