MTHFR and TYMS genotypes influence TPMT activity and its differential modulation in males and females

作者：Karas Kuzelicki Natasa^*; Milek Miha; Mlinaric Rascan Irena

来源：Clinical Biochemistry, 2010, 43(1-2): 37-42.

DOI：10.1016/j.clinbiochem.2009.09.003

• TPMT
• MTHFR
• TYMS
• Pharmacogenetics
• 6-mercaptopurine

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.

• 出版日期2010-1