Dataset Information

Folic acid supplementation dysregulates gene expression in lymphoblastoid cells

ABSTRACT: To prove our hypothesis that excess folic acid supplementation is responsible for widespread gene expression changes during gestational development that may be responsible for abnormal behaviors later on in the life, we have used whole genome microarray expression profiling in lymphoblstoid cells as a proof of concept. Human lymphoblastoid cells in culture were supplemented with folic acid, and four days later gene expression changes were measured. Expression of three genes (FMR1, GPR37L1 and TSSK3) from this data was confirmed by Western blot analyses. Dysregulation of other genes (ARHGAP6, EF1A1, MEST, SMAD3) was confirmed by qRT-PCR. Lymphoid cells at confluence were grown with or without folic acid for four days. Total mRNA was prepared and labeled with cyanine-3 (Cy3), followed by hybridization. RNA samples from three independent experiments were pooled.

OTHER RELATED OMICS DATASETS IN: PRJNA140343

ORGANISM(S): Homo sapiens

SUBMITTER: W T Brown Raju K Pullarkat Mohammed A Junaid Mohammed A. Junaid Salomon Kuizon

PROVIDER: E-GEOD-29141 | ArrayExpress | 2011-08-23

SECONDARY ACCESSION(S): GSE29141PRJNA140343

REPOSITORIES: GEO, ArrayExpress

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 5

Publications

Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition.

Junaid Mohammed A MA Kuizon Salomon S Cardona Juan J Azher Tayaba T Murakami Noriko N Pullarkat Raju K RK Brown W Ted WT

Biochemical and biophysical research communications 20110816 4

For over a decade, folic acid (FA) supplementation has been widely prescribed to pregnant women to prevent neural tube closure defects in newborns. Although neural tube closure occurs within the first trimester, high doses of FA are given throughout pregnancy, the physiological consequences of which are unknown. FA can cause epigenetic modification of the cytosine residues in the CpG dinucleotide, thereby affecting gene expression. Dysregulation of crucial gene expression during gestational deve ...[more]

PMID: 21867686

Similar Datasets

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. Overall design: A randomized, placebo-controlled intervention trial was used to study the effects of long-term supplementation (2 year) with folic acid (400 µg/day) and vitamin B12 (500 µg/day) on DNA methylation in elderly subjects. This entry contains the DNA methylation data of DNA isolated from buffy coats collected before and after the intervention with folic acid / vitamin B12 or placebo.

Project description:Genes, infection, malnutrition, and other factors affecting fetal brain development are a major component of risk for a child's emotional development and later mental illnesses, including schizophrenia, bipolar disorder, and autism. Prenatal interventions to ameliorate that risk have yet to be established for clinical use. A systematic review of prenatal nutrients and childhood emotional development and later mental illness was performed. Randomized trials of folic acid, phosphatidylcholine, and omega-3 fatty acid supplements assess effects of doses beyond those adequate to remedy deficiencies to promote normal fetal development despite genetic and environmental risks. Folic acid to prevent neural tube defects is an example. Vitamins A and D are currently recommended at maximum levels, but women's incomplete compliance permits observational studies of their effects. Folic acid and phosphatidylcholine supplements have shown evidence for improving childhood emotional development associated with later mental illnesses. Vitamins A and D decreased the risk for schizophrenia and autism in retrospective observations. Omega-3 fatty acid supplementation during early pregnancy increased the risk for schizophrenia and increased symptoms of attention deficit hyperactivity disorder, but in later pregnancy it decreased childhood wheezing and premature birth. Studies are complicated by the length of time between birth and the emergence of mental illnesses like schizophrenia, compared with anomalies like facial clefts identified at birth. As part of comprehensive maternal and fetal care, prenatal nutrient interventions should be further considered as uniquely effective first steps in decreasing risk for future psychiatric and other illnesses in newborn children. [AJP at 175: Remembering Our Past As We Envision Our Future July 1959: Longitudinal Observations of Biological Deviations in a Schizophrenic Infant Barbara Fish described the course of an infant born with fluctuating motor problems who developed schizophrenia. (Am J Psychiatry 1959; 116:25-31 )].

Project description:UNLABELLED:Child eating behaviors play an important role in nutrient intake, ultimately affecting child growth and later outcomes in adulthood. The study assessed the effects of iron-folic acid and zinc supplementation on child temperament and child eating behaviors in rural Nepal. Children (N = 569) aged 4-17 months in Sarlahi district, southern Nepal were randomized to receive daily supplements of placebo, iron-folic acid, zinc, or zinc plus iron-folic acid and followed for approximately 1 year. At baseline and four follow-up visits mothers completed questionnaires including information on demographic characteristics and child temperament and eating behaviors. The main effects of zinc and iron-folic acid supplementation on temperament and eating behaviors were assessed through crude and adjusted differences in mean cumulative score changes between visits 1 and 5. The adjusted rate-of-change for these outcomes was modeled using generalized estimating equations. Mean changes in temperament scores and in eating behavior scores between visits 1 and 5 were not significant in either the zinc or non-zinc group. Children in the iron-folic acid group increased temperament scores by 0.37 points over 5 visits (95% CI 0.02, 0.7), which was not significant after adjustment. Neither the adjusted rate-of-change in temperament scores between zinc and non-zinc (? = -0.03, 95% CI -0.3, 0.2) or iron-folic acid and non-iron-folic acid (? = 0.08, 95% CI -0.2, 0.3) were significantly different. Adjusted rate of change analysis showed no significant difference between zinc and non-zinc (? = -0.14, 95% CI -0.3, 0.04) or between iron and non-iron eating behavior scores (? = -0.11, 95% CI -0.3, 0.1). Only among children with iron-deficiency anemia at baseline was there a significant decrease in eating behavior score, indicating better eating behaviors, when supplemented with zinc (? = -0.3, 95% CI -0.6, -0.01), Ultimately, this effect of zinc on eating behaviors was the only effect we observed after approximately one year of micronutrient supplementation. TRIAL REGISTRATION:ClinicalTrials.gov NCT00109551.

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-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 ?g folic acid and 500 ?g vitamin B12 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.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.

			Action	DRS
	E-GEOD-29141.README.txt	Txt
	E-GEOD-29141.idf.txt	Idf
	E-GEOD-29141.processed.1.zip	Processed
	E-GEOD-29141.raw.1.zip	Raw
	E-GEOD-29141.sdrf.txt	Txt