RESUMO
CONTEXT: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms, mainly the C677T, have been implicated as risk factors for several cancers as the acute lymphoblastic leukemia (ALL). In addition, a potential effect of such variant on the efficacy of methotrexate (MTX) has been reported. OBJECTIVE: In this study, we evaluated the impact of the C677T variant of MTHFR on MTX-related toxicity in ALL patients from Tunisia; to provide new insights for a personalized therapy based on the human genotype. MATERIALS AND METHODS: Genotyping was carried out with restriction fragment length polymorphism (RFLP) on blood samples from a total of 35 younger patients; suffering from ALL. RESULTS: In the ALL patients, the MTHFR 677CT genotype confers a greater risk of toxicity with 1.3 times as relative risk mainly the hepatic toxicity when compared with MTHFR 677CC. CONCLUSION: Our findings suggest that C677T polymorphism of MTHFR seems to be a good marker for MTX-related toxicity in ALL.
Assuntos
Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Lactente , Masculino , Polimorfismo Genético , Adulto JovemRESUMO
BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR; NM_005957.4) is the key enzyme for folate metabolism which plays in DNA biosynthesis and the epigenetic process of DNA methylation. MTHFR gene polymorphisms, the c. 677C>T and c. 1298A>C have been implicated as risk factors for several types of cancers as the acute leukemia. AIM: We have optimized a duplex polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP) for the simultaneous detection of both variants in acute leukemia patients, from Tunisia. METHODS: Genomic DNA was extracted from EDTA-anticoagulant blood samples from a total of 50 patients suffering from acute leukemia (AL). After DNA extraction, the polymerase chain reaction using specific primers, designed using Primer 3 Software. Restriction Fragment Length Polymorphism (RFLP) was performed in two separate tubes followed by agarose gel electrophoresis. CONCLUSION: This new method has proved to be a rapid, simple, and reliable method that should facilitate high throughput genotyping of MTHFR polymorphisms in acute leukemia.