Genome-wide DNA methylation profiles of maternal peripheral blood and placentas: potential risk factors for preeclampsia and validation of GRK5
| Autor: | Dae Sim Lee, Young Nam Kim, Jeong Hyun Kim, Hyoung Doo Shin, Hyun Sub Cheong |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Genetics Regulation of gene expression Microarray analysis techniques Placentation Methylation Biology Biochemistry Andrology 03 medical and health sciences 030104 developmental biology medicine.anatomical_structure CpG site Placenta DNA methylation medicine Epigenetics Molecular Biology |
| Zdroj: | Genes & Genomics. 39:197-206 |
| ISSN: | 2092-9293 1976-9571 |
| Popis: | Hypoxic placentation has been considered as a key step for the development of preeclampsia (PE); however, the underlying epigenetic mechanisms are still not fully understood. The purpose of this study is to investigate the whole genome DNA methylation status of PE. A microarray analysis using the Infinium HumanMethylation450 BeadChip assay in the placentas and maternal peripheral blood (PB) from PE patients and normal controls was performed. For validation, a quantitative RT-PCR analysis was used. Maternal PB showed 71 differentially methylated CpG loci (44 hypermethylated and 27 hypomethylated), while placenta revealed 365 loci (37 hypermethylated and 328 hypomethylated) at the statistical significance level of |Δβ| ≥ 0.17 and P ≤ 0.01. Notably, among the candidates showing significant signals, GRK5 (a member of G protein-coupled receptor kinase family that has previously been known to be associated with PE) showed a significantly hypomethylated level in the placentas of PE patients (Δβ = −0.176, P = 2.8 × 10−5). In the validation for the potential effect of GRK5 methylation on the gene regulation, GRK5 expression was significantly increased in the placentas from PE patients compared to those from controls (P = 0.027). In further GO analysis, genes of MHC class II protein complex showed the most significant differential methylation in the maternal PB of PE patients, while genes of palate development were differentially methylated in the placenta. Although further replication and functional studies are required, our preliminary results suggest that PE has distinct DNA methylation profiles in the maternal PB and placentas, which may provide insight into future research. |
| Databáze: | OpenAIRE |
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