Abstract
We evaluated the effect of folic acid supplementation and withdrawal on DNA methylation at 1505 loci in 802 genes using bead array technology. Blood samples from 95 Chinese women (stratified by three methylenetetrahydrofolate reductase [MTHFR] genotypes) participating in a double‐blind randomized trial of folic acid supplementation (100, 400, 4000 μg/d) were screened for changes in DNA methylation level and pattern at five time points: baseline, 1, 3 and 6 months supplementation and after a 3 month withdrawal. The overall mean baseline methylation patterns were highly correlated among the three MTHFR genotypes (r2 > 0.99). At baseline greater than 99.4% of these loci had variation in mean betas (ratio of methylated/unmethylated) of less than ±0.05 differences between the three MTHFR genotypes. After supplementation the variation among individuals in locus‐specific DNA methylation levels increased compared to the variation at baseline. Analysis is underway to determine if these changes are dependent on MTHFR genotype and time. Pyrosequencing will be completed to confirm any changes in loci detected through this screen. We did not find widespread DNA methylation changes associated with folic acid supplementation however, follow‐up of a limited number of changes is underway. This work was supported by a collaborative CDC agreement and the GCRC Grant # MO1‐RR00082.
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