Natasa Karas-Kuzelicki1, Miha Milek, Irena Mlinaric-Rascan. 1. Clinical Biochemistry and Laboratory Medicine, Faculty of Pharmacy, University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia. natasa.karas@ffa.uni-lj.si
Abstract
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. Copyright 2009 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
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. Copyright 2009 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
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