Epigenetic alterations in folate transport genes in placental tissue from fetuses with neural tube defects and in leukocytes from subjects with hyperhomocysteinemia.
Epigenetic alterations in folate transport genes in placental tissue from fetuses with neural tube defects and in leukocytes from subjects with hyperhomocysteinemia.
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DOI：
10.4161/epi.23988
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发表时间：
2013-03
期刊：
影响因子：
3.7
通讯作者：
Nilsson TK
中科院分区：
文献类型：
--
作者：
Farkas SA;Böttiger AK;Isaksson HS;Finnell RH;Ren A;Nilsson TK
本研究的目的是鉴定胎盘组织中与白细胞、正常婴儿或神经管缺陷（NTDs）胎盘组织中叶酸转运基因的组织特异性差异甲基化区域（T-DMR）。利用焦磷酸测序技术，我们对叶酸受体α (FOLR1)、质子偶联叶酸转运蛋白（PCFT）和叶酸载体1 （RFC1）基因的CpG岛（CGI）和CGI海岸区进行了甲基化分析。每个基因的T-DMRs位置不同，甲基化差异在2%到54%之间。较高的T-DMR甲基化分数与较低的FOLR1和RFC1基因mRNA水平相关。在NTD病例和高血浆同型半胱氨酸（tHcy）受试者的白细胞中，根据RFC1 80G > A基因型，甲基化分数不同。在NTD病例和对照组之间，叶酸转运体基因的甲基化部分没有差异。我们认为T-DMRs参与了FOLR1和RFC1基因的表达调控，RFC1 80G > A多态性对RFC1基因的DNA甲基化产生了基因-营养相互作用，并且这种相互作用在ntd患儿和高tHcy浓度的受试者中最为突出。
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.
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影响因子：
2.5
作者：
Spiegelstein, O;Mitchell, LE;Finnell, RH
通讯作者：
Finnell, RH
影响因子：
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