Little Evidence of the Protective Role of MTHFR Genetic Polymorfism in Acute Leukaemia and Down Syndrome in Brazil.

Immunomolecular and genetic markers are great tools to understand the pathway of leukemogenesis. Because of acute leukemias (ALs) commonly arise as result of DNA damage and/or DNA translocations, the polymorphism of 5,10-methylenetetrahydrofolate reductase gene (MTHFR) have been associated to reduced enzyme activity and altered distribution of cellular folate metabolites. We have determined the prevalence of MTHFR mutations C677T and A1298C in 227 children with AL from different regions of Brazil and 279 region-matched subjects as the control group. PCR-RFLP method was applied using HinfI and MboII restriction digestion to determine the MTHFR 677 and 1298 respectively. Odds ratio (OR) and 95% confidence intervals (95%CI) were used as statistics standard methods. There were 202 acute lymphoblastic leukemias (ALL) and 65 acute myeloid leukemias (AML) from three different regions of Brazil. The frequencies of the 677CC, 677CT and 677TT genotype were 57%, 33%, 10% in the ALL cases; and 51%, 40%, 9% in the controls, respectively. Whereas the frequencies of MTHFR 1298AA, 1298AC and 1298CC were 52%, 40%, 8% in the ALL cases and 61%, 32%, 7% in the controls, respectively. Also, we analyzed separately a group of Down syndrome (DS) cases that include (i) DS with AL and, (ii) DS without AL. The frequencies of the 677CC, 677CT and 677TT genotype were 2,16%, 2,37%, 0% in the DS with AL cases, and 4,31%, 3,02%, 0,22% in the DS without AL, respectively. Whereas the frequencies of MTHFR 1298AA, 1298AC, 1298CC were 2,94%, 1,05%, 0,84% in the DS with AL and 4,83%, 2,10%, 0,63% in the DS without AL, respectively. There were no differences of MTHFR C677T frequencies in both groups in overall analysis.

However, the frequency of MTHFR 677 and MTHFR 1298 genotypes differ between cases and controls in different regions of Brazil (p<0.04). The overall analysis indicates that MTHFR C677T and A1298C may confer a protective effect against childhood acute leukemia only in distinct group of cases.