The methylenetetrahydrofolate reductase (MTHFR) 677 C>T polymorphism and folate interact to influence global leukocyte DNA methylation in young Mexican American women.

Folate provides a labile source of methyl groups which may be used for cellular methylation reactions including DNA methylation. Methylation of DNA is involved in the maintenance of genomic stability, genomic imprinting and gene silencing. The methylenetetrahydrofolate reductase (MTHFR) 677 C>T variant and race/ethnicity are important determinants of folate nutriture and may influence DNA methylation. To examine the influence of MTHFR 677 C>T polymorphism and race/ethnicity (Caucasian vs. African American) on global leukocyte DNA methylation, Mexican American (n=43; 14 CC, 12 CT and 17 TT), Caucasian (n= 14 CC) and African American (n=14 CC) consumed a folate restricted diet (135 mcg DFE/d) for 7 wk followed by folate treatment with 400 or 800 mcg DFE/d for 7 wk. Throughout the study duration, DNA methylation was not influenced by race/ethnicity. However, a week by MTHFR genotype interaction was detected (P=0.001) whereby DNA methylation declined throughout the final seven weeks of the protocol only in women with the MTHFR 677 TT genotype. Folate treatment (ie., 400 vs 800 mcg DFE/d) did not influence global leukocyte DNA methylation. These data suggest that folate and the MTHFR 677 C>T genetic variant interact to influence global leukocyte DNA methylation and that global leukocyte DNA methylation does not differ between young Caucasian and African American women. Supported by the National Institutes of Health grant S06GM53933 and funds from the California Agricultural Research Initiative.