title: Altered methylation of IGF2 DMR0 is associated with neural tube defects.
abstract: 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.
authors.affiliation: Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, No. 2, Yabao Road, Chao Yang District, Beijing 100020, People's Republic of China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Wu
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Shaofang
authors.initials: S
authors.lastname: Shangguan
authors.forename: Shaoyan
authors.initials: S
authors.lastname: Chang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Lu
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Wang
authors.forename: Huizhi
authors.initials: H
authors.lastname: Zhao
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Jin
authors.initials: J
authors.lastname: Guo
authors.forename: Bo
authors.initials: B
authors.lastname: Niu
authors.forename: Jingzhu
authors.initials: J
authors.lastname: Guo
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
mesh_terms: D001483:Base Sequence; D001921:Brain / Q000196:embryology / Q000378:metabolism; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D005333:Fetus / Q000196:embryology / Q000378:metabolism; D005865:Gestational Age; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008168:Lung / Q000196:embryology / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009436:Neural Tube Defects / Q000235:genetics*; D010920:Placenta / Q000196:embryology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012307:Risk Factors; D012737:Sex Factors; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D007335:Insulin-Like Growth Factor II