Dataset Information

Hypomethylation of serum blood clot DNA, but not plasma EDTA-blood cell pellet DNA, from vitamin B12-deficient subjects.

ABSTRACT: Vitamin B12, a co-factor in methyl-group transfer, is important in maintaining DNA (deoxycytidine) methylation. Using two independent assays we examined the effect of vitamin B12-deficiency (plasma vitamin B12<148 pmol/L) on DNA methylation in women of childbearing age. Coagulated blood clot DNA from vitamin B12-deficient women had significantly (p<0.001) lower percentage deoxycytidine methylation (3.23±0.66%; n?=?248) and greater [3 H]methyl-acceptance (42,859±9,699 cpm; n?=?17) than DNA from B12-replete women (4.44±0.18%; n?=?128 and 26,049±2,814 cpm; n?=?11) [correlation between assays: r?=?-0.8538; p<0.001; n?=?28]. In contrast, uncoagulated EDTA-blood cell pellet DNA from vitamin B12-deficient and B12-replete women exhibited similar percentage methylation (4.45±0.15%; n?=?77 vs. 4.47±0.15%; n?=?47) and [3 H]methyl-acceptance (27,378±4,094 cpm; n?=?17 vs. 26,610±2,292 cpm; n?=?11). Therefore, in simultaneously collected paired blood samples, vitamin B12-deficiency was associated with decreased DNA methylation only in coagulated samples. These findings highlight the importance of sample collection methods in epigenetic studies, and the potential impact biological processes can have on DNA methylation during collection.

SUBMITTER: Quinlivan EP

PROVIDER: S-EPMC3681792 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Hypomethylation of serum blood clot DNA, but not plasma EDTA-blood cell pellet DNA, from vitamin B12-deficient subjects.

Quinlivan Eoin P EP Crider Krista S KS Zhu Jiang-Hui JH Maneval David R DR Hao Ling L Li Zhu Z Rasmussen Sonja A SA Berry R J RJ Bailey Lynn B LB

PloS one 20130613 6

Vitamin B12, a co-factor in methyl-group transfer, is important in maintaining DNA (deoxycytidine) methylation. Using two independent assays we examined the effect of vitamin B12-deficiency (plasma vitamin B12<148 pmol/L) on DNA methylation in women of childbearing age. Coagulated blood clot DNA from vitamin B12-deficient women had significantly (p<0.001) lower percentage deoxycytidine methylation (3.23±0.66%; n = 248) and greater [3 H]methyl-acceptance (42,859±9,699 cpm; n = 17) than DNA from B ...[more]

PMID: 23785415

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Project description:Folate, and its synthetic form folic acid, function as donor of one-carbon units and have been, together with other B-vitamins, implicated in programming of epigenetic processes such as DNA methylation during early development. To what extent regulation of DNA methylation can be altered via B-vitamins later in life, and how this relates to health and disease, is not exactly known. The aim of this study was to identify effects of long-term supplementation with folic acid and vitamin B12 on genome-wide DNA methylation in elderly subjects. This project was part of a randomized, placebo-controlled trial on effects of supplemental intake of folic acid and vitamin B12 on bone fracture incidence (B-PROOF study). Participants with mildly elevated homocysteine levels, aged 65-75 years, were randomly assigned to take 400 µg folic acid and 500 µg vitamin B12 per day or a placebo during an intervention period of two years. DNA was isolated from buffy coats, collected before and after intervention, and genome-wide DNA methylation was determined in 87 participants (n=44 folic acid/vitamin B12, n=43 placebo) using the Infinium HumanMethylation450 BeadChip. After intervention with folic acid and vitamin B12, 162 (versus 14 in the placebo group) of the 431,312 positions were differentially methylated as compared to baseline. Comparisons of the DNA methylation changes in the participants receiving folic acid and vitamin B12 versus placebo, revealed one single differentially methylated position (cg19380919) with a borderline statistical significance. However, based on the analyses of differentially methylated regions (DMRs) consisting of multiple positions, we identified 6 regions that differed statistically significantly between the intervention and placebo group. Pronounced changes were found for regions in the DIRAS3, ARMC8 and NODAL genes, implicated in carcinogenesis and early embryonic development. Furthermore, serum levels of folate and vitamin B12 or plasma homocysteine were related to DNA methylation of 173, 425 and 11 regions, respectively. Interestingly, for several members of the developmental HOX genes, DNA methylation was related to serum levels of folate. Long-term supplementation with folic acid and vitamin B12 in elderly subjects resulted in effects on DNA methylation of several genes, among which genes implicated in developmental processes.

Dataset Information

Hypomethylation of serum blood clot DNA, but not plasma EDTA-blood cell pellet DNA, from vitamin B12-deficient subjects.

Publications

Hypomethylation of serum blood clot DNA, but not plasma EDTA-blood cell pellet DNA, from vitamin B12-deficient subjects.

Similar Datasets

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