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Analysis of locus‐specific DNA methylation in response to chronic folic acid supplementation and withdrawal in chinese women
Author(s) -
Brant Jason O.,
Zhu Jianghui,
Quinlivan Eoin,
Crider Krista,
Berry R. J.,
Ling Hao,
Zhu Li,
Maneval David,
Bailey Lynn B.,
Yang Thomas P.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.724.8
Subject(s) - dna methylation , methylation , cpg site , methylenetetrahydrofolate reductase , bisulfite sequencing , pyrosequencing , biology , genotype , microbiology and biotechnology , medicine , endocrinology , genetics , dna , gene , gene expression
The objective of this study was to evaluate the effect of chronic folic acid supplementation and withdrawal on DNA methylation at specific loci in a Chinese population not previously exposed to dietary folic acid. Women of reproductive age were assigned a daily folic acid intake of 400 µg for 6 mo, and whole blood samples were drawn prior to supplementation, after 6 mo of continuous daily folic acid intake, and 3 mo after folic acid supplementation was withdrawn. Blood DNA from 5 CC and 5 TT MTHFR 677C→ T genotype subjects was randomly chosen and analyzed for changes in DNA methylation. Previous analysis of global DNA methylation levels demonstrated a significant reduction in methylation after 6 months of supplementation, with an additional decrease after 3 months of withdrawal. To further characterize this decrease in global DNA methylation, the L1 repetitive element and the imprinted SNRPN promoter were analyzed by high resolution sodium bisulfite genomic sequencing (BGS) for changes in DNA methylation. Our preliminary data show a near complete loss of methylation at the SNRPN promoter at 6 and 9 months. Methylation levels of L1 elements showed a trend toward loss of methylation during supplementation and after withdrawal. To further assess potential changes in DNA methylation, additional loci are being analyzed by BGS and pyrosequencing. Supported by a collaborative CDC agreement and GCRC Grant # MO1‐RR00082.