Altered methylation of IGF2 DMR0 is associated with neural tube defects

Neural tube defects (NTDs) are serious congenital malformation of fusion failure of the neural tube during early embryogenesis. DNA methylation disorders have been found in NTD-affected fetuses, and are correlated to the risk of NTDs. The insulin-like growth factor 2 (IGF2) gene, maternally imprinte...

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Veröffentlicht in:Molecular and cellular biochemistry 2013-08, Vol.380 (1-2), p.33-42
Hauptverfasser: Wu, Lihua, Wang, Li, Shangguan, Shaofang, Chang, Shaoyan, Wang, Zhen, Lu, Xiaolin, Zhang, Qin, Wang, Jianhua, Zhao, Huizhi, Wang, Fang, Guo, Jin, Niu, Bo, Guo, Jingzhu, Zhang, Ting
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Sprache:eng
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Zusammenfassung:Neural tube defects (NTDs) are serious congenital malformation of fusion failure of the neural tube during early embryogenesis. DNA methylation disorders have been found in NTD-affected fetuses, and are correlated to the risk of NTDs. The insulin-like growth factor 2 (IGF2) gene, maternally imprinted, has a key role in fetal development. IGF2 transcription is partly controlled by differentially methylated regions (DMRs) 0 and 2. To assess whether disturbed methylation pattern increases the incidence of NTDs, we employed matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to quantify CpG methylation levels of DMR2 and 0 in fetuses with or without NTDs. We found that the methylation level of IGF2 DMR0 increased significantly in the brain tissues of NTD-affected fetuses. And hypermethylation of DMR0 was associated with an increased risk of NTDs, with an odds ratio of 5.375 (95 % CI: 1.447–19.965; p  = 0.007) . IGF2 mRNA expression was negatively correlated with the methylation level of DMR0 ( R 2  = 0.893; p  = 0.000) in HCT15 cells. These results highlights that IGF2 DMR0 hypermethylation is a potential risk factor of NTD, and IGF2 gene is a promising candidate gene to study for a greater understanding of the cause of NTDs.
ISSN:0300-8177
1573-4919
DOI:10.1007/s11010-013-1655-1