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

[Guest guest]

More concerns about folic acid supplementation in pregnancy:

Folic acid supplementation dysregulates gene expression in

lymphoblastoid cells--implications in nutrition.

<http://www.ncbi.nlm.nih.gov/pubmed/21867686>

Junaid MA, Kuizon S, Cardona J, Azher T, Murakami N, Pullarkat RK, Brown WT.

Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92.

Source

Department of Developmental Biochemistry,

New York State Institute for Basic Research in Developmental Disabilities

Staten Island, NY 10314, USA. mohammed.junaid@...

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 development may have lifelong adverse effects or lead

to neurodevelopmental defects, such as autism. We have investigated the

effect of FA supplementation on gene expression in lymphoblastoid cells

by whole-genome expression microarrays. The results showed that high FA

caused dysregulation by ≥ four-fold up or down to more than 1000 genes,

including many imprinted genes. The aberrant expression of three genes

(FMR1, GPR37L1, TSSK3) was confirmed by Western blot analyses. The level

of altered gene expression changed in an FA concentration-dependent

manner. We found significant dysregulation in gene expression at

concentrations as low as 15 ng/ml, a level that is lower than what has

been achieved in the blood through FA fortification guidelines. We found

evidence of aberrant promoter methylation in the CpG island of the TSSK3

gene. Excessive FA supplementation may require careful monitoring in

women who are planning for, or are in the early stages of pregnancy.

Aberrant expression of genes during early brain development may have an

impact on behavioural characteristics.