To Explore The Effect And Significance Of Gene Polymorphism On The Metabolism And Clinical Of Methotrexate

Objective: To study the genetic polymorphisms of methylene tetrahydrofolate reductase(MTHFR)C677T,A1298 C on the dynamic metablism and clinnic effects of methotrexate(MTX)in the treatment of patients with acute lymphoblastic leukemia(ALL).Methods:Peripheral blood genomic DNA of 32 cases patients with acute lymphoblastic leukemia was extracted,and genotype polymorphisms were detected by direct sequencing of PCR fragments.The plasma concentrations of MTX were determined by high performance liquid chromatography(HPLC)after intravenous infusion of HD-MTX treatment for 24 h,48h,72 h.The side effects of MTX chemotherapy were evaluated in terms of standard of international cancer agency.Results: Difference of plasma concentration of MTX in every C677 T genotype patients after intravenous infusion of HD-MTX treatment for 24 h was significant(P<0.05).There were no significant differences of plasma concentration of MTX in every A1298 C genotype patients after intravenous infusion of HD-MTX treatment for 24 h,48h,72 h and every C677 T genotype patients after intravenous infusion of HD-MTX treatment for 48 h,72h(P>0.05).The probabilities of side reaction in carriers with MTHFR C677 T CC,TT,CT genotype were 27.27%,31.28%,40.91% respectively,the differences were statistically significant(P>0.05).But the differences of probabilities of side reaction in carriers with every A1298 C genotype had no statistical significance(P>0.05).Conclusions: The gene polymorphism of MTHFR C677 T can affect plasma concentrations of MTX of patients with ALL.The gene polymorphism of MTHFR C677 T can affect the incidence of the side effects of MTX.These results indicate that MTX chemotherapy may be adjusted by MTHFR genotype for clinical individual therapy.