Analysis of Locus‐Specific DNA Methylation in Response to Chronic Folic Acid Supplementation and Withdrawal in Chinese Women

Abstract

The objective of this study was to evaluate the effect of chronic folic acid supplementation and withdrawal on DNA methylation at specific genetic loci in a Chinese population. Women of reproductive age were assigned a daily folic acid supplement of 400 μg for 6 months, and whole blood samples were drawn at baseline, after 6 months of daily folic acid intake, and 3 months after folic acid supplementation was withdrawn. Blood DNA from 10 subjects (5 MTHFR CC and 5 TT) was analyzed by methylation‐specific PCR (MSP) for changes in methylation status at the promoters of 6 tumor suppressor genes: DAPK, ESR1, HIC1, MGMT, p16, and TIMP, genes known to be aberrantly silenced by hypermethylation of their promoter regions in a variety of human cancers. Overall, no widespread changes in normal DNA methylation patterns (i.e., hypermethylation) were detected for any of the genes tested in all 10 subjects in response to 6 months of folic acid supplementation and 3 months of folic acid withdrawal. To further assess potential changes in DNA methylation in response to folic acid fortification, additional tumor suppressor genes are being analyzed by MSP, and high resolution DNA methylation analyses by sodium bisulfite genomic sequencing are currently in progress. Supported by a collaborative CDC agreement.