Methylenetetrahydrofolate reductase: a link between folate and riboflavin?
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Folic Acid↗
Biomedical subjects
Rima Rozen
Publications and source records attributed to Rima Rozen.
Studies of methionine cycle intermediates (SAM, SAH), DNA methylation and the impact of folate deficiency on tumor numbers in Min mice.
Several epidemiological studies have suggested a modulatory effect of dietary folate intake on the risk of colorectal cancer. The molecular basis for this inverse association is not clearly understood, but may involve alterations in DNA methylation. In this study, we examined the levels of methylation intermediates [S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH)] and of global DNA methylation in the pre-neoplastic small intestine of Min (multiple intestinal neoplasia) mice. We also studied the effect of folate/choline deficiency on these parameters and on tumor multiplicity in this animal model. In folate-adequate Min mice, we identified positive linear correlations between SAM or SAH and tumor numbers (R(2) = 0.38, P < 0.005; R(2) = 0.26, P = 0.025, respectively). A positive correlation between global DNA hypomethylation and tumor multiplicity was also observed (R(2) = 0.29, P = 0.014). These three biochemical determinants (SAM, SAH and DNA hypomethylation) may, therefore, serve as early markers of cell transformation. Folate/choline deficiency, however, did not produce a consistent effect on tumor numbers in three separate experiments. As an increase in tumor numbers was observed only in folate- and choline-deficient mice with low levels of SAM and DNA hypomethylation, the modulatory role of folate may be dependent on the transformation state of the cell.
Animals↗
Spina bifida, folate metabolism, and dietary folate intake in a Northern Canadian aboriginal population.
OBJECTIVES: Inhabitants of the subarctic region of the Eastern James Bay of Northern Quebec consume a diet low in folate. This is largely secondary to poor access to plant-foods and a preferred diet high in meat, fowl, and fish as in many other northern populations. Furthermore, there is a high frequency of spina bifida in the Cree of the region. It was hypothesized that genetically altered folate metabolism as well as low folate intake contributes to the high frequency of spina bifida. METHODS: A case-control study evaluating folate metabolism and the common 677C-T polymorphism of the gene for methylenetetrahydrofolate reductase (MTHFR) in mothers of children with spina bifida, and controls (n=23) of Cree descent from the Eastern James Bay region. These results were compared to a similar Montreal cohort (n=152) who were not of First Nations descent. Dietary intake of folate of 219 women of the Eastern James Bay region was also determined. RESULTS: No Cree mothers of children with spina bifida were homozygous for the 677C-T polymorphism of MTHFR. Although serum cobalamin was significantly higher in Cree mothers, RBC folate was significantly lower than in the Montreal cohort. In addition, plasma homocysteine was significantly lower in the Cree. Dietary intake of folate of women in the same region was substantially lower (100 microg/day) than widely recommended daily intakes. CONCLUSIONS: In this remote Canadian aboriginal community there is no evidence of altered folate metabolism in the mothers of children with spina bifida. Nonetheless, it remains essential that culturally appropriate public health efforts be continued to increase the intake of folic acid in the hope of reducing the high frequency of spina bifida in this population.
Adult↗