Influence of the methylenetetrahydrofolate reductase in the pathogenesis of the childhood acute leukemia

Abstract

ILeukemia is a result of an adverse gene-environment interaction, with a susceptibility related to polymorphisms. Since the methylenetetrahydrofolate reductase (MTHFR) plays a key role in folate metabolism, changes in its activity (resulting from polymorphisms) or changes in folate supply could influence DNA synthesis, repair and methylation. In this work, we have determined the frequency of MTHFR 677C>T and 1298A>C polymorphisms in 177 children, with acute leukemia aged less than 16 years, from different regions of Brazil. Two hundred and fourty-nine region-matched subjects were the control group. PCR-RFLP method was used for genotyping. The frequencies for 677CC, 677CT and 677TT genotypes were 51%, 40%, 9% for controls; 57%, 33%, 10% for acute linfoblastic leukemia (ALL) cases, and 49%, 39%, 12% for acute myeloid leukemia (AML) cases, respectively. The frequencies of MTHFR 1298AA, 1298AC, and 1298CC were 62%, 31%, 7% for controls, 51%, 41%, 8% for ALL cases, and 67%, 31%, 2% for AML cases, respectively. We compared cases and controls for 677C>T polymorphism, the OR was 0,7 (0,5 - 1,2) and 1,0 (0,4 - 2,1) for CT and TT genotypes, respectively. The OR was 1,6 (1,0 -2,5) and 1,3 (0,6 - 3,0) for AC and CC genotypes, respectively. In AML cases, the OR was 1,0 (0,5 - 2,1) for CT genotype, and 1,3 (0,5 - 3,9) for TT genotypes. The OR was 0,9 (0,4 - 1,9) and 0,3 (0,04 - 2,3) for AC and CC genotypes, respectively. No significant difference was observed when MTHFR 677C>T and 1298A>C polymorphisms were compared between case and control groups. The statistical analysis suggests that MTHFR 677C>T and 1298A>C polymorphisms do not have a protective effect against childhood acute leukemia.