Related Experiment Video
Updated: Jan 9, 2026

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer
Published on: May 10, 2024
MTHFR and TYMS genotypes influence TPMT activity and its differential modulation in males and females
Natasa Karas-Kuzelicki1, Miha Milek, Irena Mlinaric-Rascan
1Clinical Biochemistry and Laboratory Medicine, Faculty of Pharmacy, University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia. natasa.karas@ffa.uni-lj.si
Objectives:
TPMT catalyzes the deactivation of the cytostatic drug 6-mercaptopurine used in treatment of cancer. Patients with low levels of TPMT more often experience severe toxic effects when treated with standard doses of 6-mercaptopurine than patients with high levels who, in turn, may experience inadequate treatment. It is therefore very important to assess factors that could influence TPMT activity.
Design And Methods:
Red blood cell TPMT activity was measured by means of HPLC and genotypes of 86 healthy individuals were analyzed using TaqMan and PCR-RFLP methods, in order to investigate the effect of TPMT, MTHFR and TYMS genotypes on TPMT activity.
Results:
TPMT activity was higher in TPMT wild-type males than females (p=0.028). Three-way ANOVA interaction analysis revealed a significant interaction effect between MTHFR genotype and gender on TPMT activity (p=0.023).
Conclusion:
Males have higher TPMT activity than females and the trend of influence of MTHFR genotype on TPMT activity is different in the two gender groups.
Related Concept Videos
X-linked Traits
Therapeutic Drug Monitoring: Affecting Factors
Factors Affecting Drug Biotransformation: Biological
Species differences: Variations in enzyme systems across species can cause disparities in drug metabolism. For instance, humans may metabolize certain drugs faster than rodents, altering therapeutic effects.
Strain differences: Genetic variations within a species can result in differing enzyme activity, impacting drug response and toxicity. For example, some mouse strains may...
Human Genetics
The complex relationship between genetics and psychology is observable through common biological components such...
Background and Environment Affect Phenotype
An example of how genetic background affects phenotype can be seen in horses. The Extension gene in horses is responsible for their coat color. A wild-type gene (EE) produces black pigment in the coat, while a mutant gene (ee) produces red pigment. A...
Epistasis

