期刊
CLINICAL EPIGENETICS
卷 7, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s13148-015-0154-5
关键词
DNA methylation; Folic acid; Vitamin B-12; B-vitamins; One-carbon metabolism; Intervention trial; Infinium 450k BeadChip; Elderly; Cancer; Development; Epigenetics
资金
- World Cancer Research Fund (WCRF) NL
- WCRF International [WCRF 2009/68]
- Netherlands Organization for Health Research and Development (ZonMw), the Hague, the Netherlands [6130.0031]
- NZO (Dutch Dairy Association), Zoetermeer, the Netherlands
- NCHA (Netherlands Consortium Healthy Ageing) Leiden/Rotterdam, the Netherlands
- Ministry of Economic Affairs, Agriculture and Innovation, the Hague, the Netherlands [KB-15-004-003]
- Wageningen University, Wageningen, the Netherlands
- VU University Medical Center, Amsterdam, the Netherlands
- Erasmus MC, Rotterdam, the Netherlands
- Alpe d'Huzes/Dutch Cancer Society [2011-5234]
Background: 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 B-12 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 B-12 on bone fracture incidence (B-vitamins for the PRevention Of Osteoporotic Fractures (B-PROOF) study). Participants with mildly elevated homocysteine levels, aged 65-75 years, were randomly assigned to take 400 mu g folic acid and 500 mu g vitamin B-12 per day or a placebo during an intervention period of 2 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. Results: After intervention with folic acid and vitamin B-12, 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 B-12 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 B-12 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. Conclusions: Long-term supplementation with folic acid and vitamin B-12 in elderly subjects resulted in effects on DNA methylation of several genes, among which genes implicated in developmental processes.
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