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


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).


CONCLUSIONS
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.
Karas-Kuzelicki
Natasa
N
Clinical Biochemistry and Laboratory Medicine, Faculty of Pharmacy, University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia. natasa.karas@ffa.uni-lj.si
Milek
Miha
M
Mlinaric-Rascan
Irena
I
D000293:Adolescent; D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism / Q000627:therapeutic use; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D015122:Mercaptopurine / Q000378:metabolism / Q000627:therapeutic use; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D012737:Sex Factors; D013940:Thymidylate Synthase / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
D000964:Antimetabolites, Antineoplastic; D005492:Folic Acid; D015122:Mercaptopurine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008780:Methyltransferases; D013940:Thymidylate Synthase; C022745:thiopurine methyltransferase