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| EWAS ID | EWAS590 |
| GSE ID | GSE69502 |
| EWAS Title | Profiling placental and fetal DNA methylation in human neural tube defects |
| Disease/Phenotype | neural tube defects (NTDs) |
| Group1 | brain |
| Group2 | chorionic villi |
| Group1 Sample Size | 20 |
| Group2 Sample Size | 52 |
| Summary | The incidence of neural tube defects (NTDs) declined by about 40% in Canada with the introduction of national folic acid (FA) fortification programs. However, NTDs persist despite the fact that few Canadians currently exhibit folate deficiency. FA fortification may have aided in reducing NTDs by overcoming abnormal one carbon metabolism cycling, the process which provides one carbon units for methylation of DNA. We considered that NTDs persisting in a folate replete population may also occur in the context of compromised one carbon metabolism, and that this might manifest as abnormal DNA methylation (DNAm). Second trimester human placental chorionic villi, kidney, spinal cord, brain and muscle were collected from 19 control, 22 spina bifida and 15 anencephaly fetuses in British Columbia, Canada. DNA was extracted, assessed for methylenetetrahydrofolate reductase (MTHFR) genotype and for genome-wide DNAm using repetitive elements, in addition to the Illumina Infinium HumanMethylation450 (450k) array. No difference in repetitive element DNAm was noted. Using a false discovery rate <0.05 and average group difference in DNAm >0.05, differentially methylated array sites were only identified in (i) the comparison of anencephaly to controls in chorionic villi (n=4 sites) and (ii) the comparison of spina bifida to controls in kidney (n=3,342 sites). We suggest that the distinctive DNAm of spina bifida kidneys may be consequent to the neural tube defect. Although other studies have provided data to support altered DNAm in NTDs, this was not a major feature of British Columbian cases on a genome-wide or site specific level. |
| Contributor | Price EM, Peñaherrera MS, Portales-Casamar E, Pavlidis P, Van Allen MI, McFadden DE, Robinson WP |
| Public date | Public on Jan 23, 2016 |
| Citation (PubMed ID) | 26889207 |
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