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No effect of folic acid depletion or repletion on leukocyte DNA methylation overall or by MTHFR 677C→T genotype in healthy individuals
Author(s) -
Elsworthy James,
Venn Bernard J,
Reeve Anthony E,
Morison Ian M,
Green Tim J
Publication year - 2007
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.21.5.a347
Subject(s) - methylenetetrahydrofolate reductase , methylation , dna methylation , genotype , homocysteine , folic acid , medicine , endocrinology , dna , chemistry , microbiology and biotechnology , biology , biochemistry , gene , gene expression
DNA methylation modulates gene expression and helps maintain genomic integrity. Folate is a primary source of methyl groups and inadequate folate status may impair DNA methylation. A common polymorphism (677C→T) in a critical enzyme involved in folate metabolism ‐ methylene tetrahydrofolate reductase (MTHFR) – has been associated with lower DNA methylation when combined with poor folate status. We aimed to assess changes in DNA methylation as a result of folic acid depletion followed by folic acid supplementation in a group of healthy people represented by all three MTHFR genotypes. Ninety‐three participants (C/C n = 33; C/T n = 33; T/T n = 32) were asked to avoid folic acid fortified foods for 12 wks (depletion) and then take a supplement containing 400 μg/d for 12 wks (repletion). Blood was collected at baseline, post‐depletion, and post‐repletion. During depletion red cell and plasma folate concentrations fell by 110 ± 151 and 6 ± 8 nmol/L, respectively (P < 0.001). During repletion red cell and plasma folate increased by 366 ± 181 and 26 ± 12 (P < 0.001), respectively, and homocysteine fell by 0.9 ± 1.9 μmol/L (P < 0.001). There were no differences in blood folate or homocysteine concentration by MTHFR genotypes. DNA methylation remained within 0.1% of the baseline value throughout the study. No difference in DNA methylation was observed among genotypes, and no variation was found under conditions of folic acid depletion or folic acid supplementation. Folic acid depletion and repletion had no effect on global DNA methylation overall or by MTHFR genotype.