TY - JOUR
T1 - The effects of long-term daily folic acid and vitamin B-12 supplementation on genome-wide DNA methylation in elderly subjects
AU - Kok, Dieuwertje E. G.
AU - Dhonukshe-Rutten, Rosalie A. M.
AU - Lute, Carolien
AU - Heil, Sandra G.
AU - Uitterlinden, André G.
AU - van der Velde, Nathalie
AU - van Meurs, Joyce B. J.
AU - van Schoor, Natasja M.
AU - Hooiveld, Guido J. E. J.
AU - de Groot, Lisette C. P. G. M.
AU - Kampman, Ellen
AU - Steegenga, Wilma T.
PY - 2015
Y1 - 2015
N2 - 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
AB - 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
U2 - https://doi.org/10.1186/s13148-015-0154-5
DO - https://doi.org/10.1186/s13148-015-0154-5
M3 - Article
C2 - 26568774
SN - 1868-7075
VL - 7
SP - 121
JO - Clinical epigenetics
JF - Clinical epigenetics
M1 - 121
ER -