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.
Keywords: 6-mercaptopurine; ALL; S-adenosyl methionine; pharmacogenetics; thiopurine-S-methyltransferase.