Epigenetic alterations in folate transport genes in placental tissue from fetuses with neural tube defects and in leukocytes from subjects with hyperhomocysteinemia |
| |
Authors: | Sanja A. Farkas Anna K. B?ttiger Helena S. Isaksson Richard H. Finnell Aiguo Ren Torbj?rn K. Nilsson Torbj?rn K. Nilsson |
| |
Affiliation: | 1.Department of Laboratory Medicine; Örebro University Hospital; Örebro, Sweden;2.School of Health and Medical Sciences; Örebro University; Örebro, Sweden;3.Department of Nutritional Sciences; Dell Pediatric Research Institute; University of Texas; Austin, TX USA;4.Institute of Reproductive and Child Health and Ministry of Health Key Laboratory of Reproductive Health; Peking University Health Science Center; Beijing, China |
| |
Abstract: | The objectives of this study were to identify tissue-specific differentially methylated regions (T-DMR’s) in the folate transport genes in placental tissue compared with leukocytes, and from placental tissues obtained from normal infants or with neural tube defects (NTDs). Using pyrosequencing, we developed methylation assays for the CpG islands (CGIs) and the CGI shore regions of the folate receptor α (FOLR1), proton-coupled folate transporter (PCFT) and reduced folate carrier 1 (RFC1) genes. The T-DMRs differed in location for each gene and the difference in methylation ranged between 2 and 54%. A higher T-DMR methylated fraction was associated with a lower mRNA level of the FOLR1 and RFC1 genes. Methylation fractions differed according to RFC1 80G > A genotype in the NTD cases and in leukocytes from subjects with high total plasma homocysteine (tHcy). There were no differences in methylated fraction of folate transporter genes between NTD cases and controls. We suggest that T-DMRs participate in the regulation of expression of the FOLR1 and RFC1 genes, that the RFC1 80G > A polymorphism exerts a gene-nutrition interaction on DNA methylation in the RFC1 gene, and that this interaction appears to be most prominent in NTD-affected births and in subjects with high tHcy concentrations. |
| |
Keywords: | FOLR1 PCFT RFC1 80G>A homocysteine tissue-specific DNA methylation GpG island NTD |
|