The methylenetetrahydrofolate reductase 677TT genotype and folate intake interact to lower global leukocyte DNA methylation in young Mexican American women

DNA methylation is an epigenetic feature associated with X chromosome inactivation, genomic imprinting, transcriptional silencing of genes, and genomic stability. Folate provides a labile source of methyl groups that may be used for cellular methylation reactions, including DNA methylation. The methylenetetrahydrofolate reductase (MTHFR) 677C→T variant is an important determinant of folate nutriture and may influence DNA methylation. This study sought to assess the influence of the MTHFR C677T genotype on global leukocyte DNA methylation in young (age range = 18-45 years) Mexican American women (N = 43: CC, n = 14; CT, n = 12; TT, n = 17). Subjects consumed a folate-restricted diet (135 μg of dietary folate equivalents per day) for 7 weeks followed by folate treatment with 400 or 800 μg of dietary folate equivalents per day for another 7 weeks. Global leukocyte DNA methylation was assessed via the cytosine extension assay at weeks 0, 7 (after folate restriction), and 14 (after folate treatment). No main effect of MTHFR C677T genotype or folate intake was detected at any time point during the study. However, at the end of folate treatment (week 14), DNA methylation was lower (P < .05) among women with the MTHFR 677TT genotype than among those with the CT or CC genotype. Because it is unlikely that folate treatment would result in methyl group loss, we suggest that there was a delay in the DNA methylation response to folate intake. Overall, these data suggest that the MTHFR 677TT genotype and folate interact to lower global leukocyte DNA methylation patterns in young Mexican American women.