From: The role of DNA methylation in syndromic and non-syndromic congenital heart disease
Study (reference) | Study population Sample type | Cohort | Sample size | Methylation measures | DNA methylation change | |
---|---|---|---|---|---|---|
[109] | Myocardial tissues (right ventricle/right atrium) | TOF: 8, VSD: 8 | Case: 16, Control: 7 | DNA methylation profiles were generated using MBD-seq | A significant overlap for hypermethylated promoters and down-regulated genes was found, and vice versa. A hypermethylated CpG island in the promoter of SCO2 was identified | |
[112] | Fetal heart tissue | 6 DS without CHD, 6 DS with CHD, 6 isolated CHD | Case: 18, Control: 4 | Global methylation profile was studied by using the Illumina Infinium Human Methylation27 array Platform | Hypermethylation of several intragenic sites at the MSX1 gene was found in iCHD Hypermethylation of the GATA4 gene was present in Down syndrome with or without congenital heart defects, as well as iCHD | |
[119] | Children (1 to 48Â months), Myocardial tissues (right ventricle) | TOF | Case: 32, Control: 15 | Sequenom MassARRAY platform was performed to examine the methylation levels of LINE-1, NKX2-5, HAND1 and TBX20 | Lower LINE-1 methylation levels are associated with increased risk of TOF. Higher methylation levels of NKX2-5 and HAND1 and lower methylation levels of TBX20 were observed in TOF patients than in controls | |
[124] | New born (24 to 79Â h), Blood | AVS | Case: 24, Control: 24 | A genome-wide DNA methylation analysis using an Illumina Infinium 450Â k human methylation assay was conducted | The study identified significantly-altered CpG methylation at 59 sites in 52 genes in AVS subjects as compared to controls, including DUSP27, RUNX1, TXNRD2, APOA5 and PCSK9 | |
[125] | New born (24 to 79Â h), Blood | TOF | Case: 24, Control: 24 | Genome-wide methylation assay used Illumina Infinium HumanMethylation450 BeadChips | 64 differentially methylated CpG sites in TOF cases were identified. Multiple differentially methylated genes are known or plausibly linked to heart development and postnatal heart disease | |
[133] | New born (24 to 72Â h), Blood | DS patients with or without CHD | DS patients with CHD: 11, without CHD: 10 | Low-pass whole genome bisulfite sequencing (WGBS) of 86 NDBS DNA was performed to examine DNA methylation profiles | A comparation of DMRs between DS with and without CHD distinguished 1588 nominally significant DMRs (35% hypermethylated, 65% hypomethylated). There was hypomethylated DMR mapped to RUNX1 in CHD | |
[49] | Blood | DORV | Monozygotic twins, Case: 1, Control: 1 | The DNA methylation pattern were analyzed using reduced representation bisulfite sequencing | Many DMR-related genes are enriched in pathways that contribute to cardiac development, such as ZIC3 and NR2F2 | |
[139] | Blood | TOF | Monozygotic twins, Case: 2, Control: 2 | Whole genome sequencing (WGS) and whole genome bisulfite sequencing (WGBS) were used to examine the genetic and epigenetic differences | Difference between the two monozygotic discordant twin pairs was observed in epigenetic alterations rather than at the genetic or structural genomic level, such as DMCs in the promoter region of the cardiac transcription factors TBX20, GATA4 and NKX2-5 | |
[12] | Blood | HLHS: 8, VSD: 8, ASD: 12, CoA: 14, PS: 14, ToF: 14 | Case: 60, Control: 32 | Genome-wide DNA methylation analysis was performed on DNA from newborn blood spots | Profound differences in cytosine methylation were observed in hundreds of genes in newborns with different types of CHD | |
[156] | Fetal skin fibroblasts | DS with CHD (VSD, ASD) | DS MZ twins discordant for CHD, Case: 4, Control: 4 | Reduced Representation Bisulphite Sequencing (RRBS) were applied to profile DNA methylation changes | 197 DMRs in monozygotic twins discordant for VSD and 88 DMRs in monozygotic twins discordant for AVSD were identified, including 13 common DMRs between two sets | |
[141] | Placenta | VSD | Case: 8, Control: 10 | Genome-wide DNA methylation assay was performed using the Illumina HumanMethylation450 BeadChip assay | Most differentially methylated genes, have been shown to be associated with heart development or disease | |
[142] | Placenta | TOF | Case: 8, Control: 10 | The Illumina Infinium HumanMethylation450 BeadChip assay was used | ARHGAP22, CDK5, TRIM27 and IER3 had outstanding predictive accuracy for the prediction of TOF. ID4, HES7 and PPP3CA, which may be associated with heart disease, also showed differential methylation in this research | |
[116] | Myocardium | TDF, VSD, DCRV | Case: 24, Control: 11 | The methylation of a BRG1 promoter was analyzed using pyrosequencing and the MassARRAY platform | BRG1 | hypomethylation |
[149] | Myocardial tissues | CHD | Case: 31, Control: 2 | BSP and MSP were used to detect the methylation in CITED2 promoter region | CITED2 | hypermethylation |
[143] | Blood | VSD, ASD, TOF, PDA, CoA, other CHDs | Case: 27, Control: 28 | Eighteen imprinted genes methylation were measured by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry | GRB10, MEST | hypermethylation |
PEG10, NAP1L5, INPP5F, PLAGL1, NESP, MEG3 | hypomethylation | |||||
[144] | Blood | CHD with EM | Case: 24, Control: 20 | The methylation levels of 3 candidate genes were analysed by the MassARRAY platform | SNRPN, ZAC1 | hypermethylation |
INPP5F | hypomethylation | |||||
[118] | Blood | AVSD, VSD | Case: 7, Control: 9 | Methylation analysis of the promoter regions was performed by means of the Human Promoter 1.0 Arrays (Affymetrix) | NRG1 | hypermethylation |