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MTHFR and TYMS genotypes influence TPMT activity and its differential modulation in males and females
Karas Kuželički, Nataša ; Milek, Miha, 1981- ; Mlinarič-Raščan, Irena
Objectives: TPMT catalyzes the deactivation of the cytostatic drug 6-mercaptopurine used in treatment of cancer. Patients with low levels of TPMTmore 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 cellTPMT 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.
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