Table 3.
DNA methylation in CHDs.
| DNA Methylation | |||||
|---|---|---|---|---|---|
| Allele | Clinical Sample Size | Modification | Tissue Type | Cardiac Disease Phenotype | Reference |
| NOX5 | 21 VSD and 15 controls | Hypermethylation | Fetal myocardial tissue | VSD | [78] |
| KIAA0310; RAB43; NDRG2 | 21 VSD and 15 controls | Hypermethylation | Fetal myocardial tissue | VSD | [79] |
| SIVA1 | Hypomethylation | ||||
| LINE-1* | 32 TOF and 15 controls [80]; 48 TOF patients and 16 controls [81] |
Hypomethylation | Right ventricular tissue samples [80]; Right ventricular outflow tracts [81] | TOF | [80] |
| NKX2.5; HAND1; EGFR; EVC2; TBX5; CFC1B | 30 TOF and 6 controls [82]; 41 TOF and 6 control [83] | Hypermethylation | Right ventricular myocardium tissues | TOF, HLHS | [82,83] |
| GATA4; MSX1 | 6 Down syndrome with CHD, 6 Down syndrome without CHD, 6 isolated heart malformations, and 4 control | Hypermethylation | Whole heart tissue | AVSD, VSD, CoA, TOF, LHH, HAA, DORV, VSD, TOF, MVA, AVA, PFO, TVS; RHH, TA; ADA; TAV | [84] |
| SCO2 | 8 TOF, 8 ventricular septal defect, and 4 control | Hypermethylation | Myocardial biopsies | TOF, VSD | [85] |
| ZFPM2 | 43 TOF and 6 controls | Hypermethylation | Right ventricular outflow tract | TOF | [86] |
| p16INK4a | 63 TOF and 75 controls | Hypermethylation | Whole blood | TOF | [87] |
| BRG1 | 24 CHD and 11 controls | Hypomethylation | Various cardiac tissues. | TOF, VSD, DCRV | [88] |
| MTHFR | 40 Down syndrome without CHD; 40 mothers of Down syndrome with CHD, and 40 age matched control mothers | Hypermethylation | Whole blood | AVSD; VSD, ASD; TOF | [89] |
| TBX20 | 23 TOF and 5 controls [90]; 42 TOF and 6 controls [91] | Hypomethylation | Right ventricular myocardial tissues | TOF | [90] |
| ZIC3; NR2F2 | Monozygotic twin pair discordant for DORV | Hypermethylation | Whole blood | DORV | [92] |
| NRG1 | 7 Down syndrome patients with CHD and 9 Down syndrome without CHD | Hypermethylation | Whole blood | Endocardial cushion-type | [93] |
* Repetitive Long Interspersed Nucleotide Element-1. Cardiac disease abbreviations: ADA (Absent Ductus Arteriosus), ASD (Atrial Septal Defects), AVA (Aortic Valve Atresia), AVSD (Atrioventricular Septal Defect), CoA (Coarctation of the pre-ductal Aorta), DCRV (Double-Chambered Right Ventricle), DORV (Double Outlet Right Ventricle), HAA (Hypoplasia of the Ascending Aorta), HLHS (Hypoplastic Left Heart Syndrome), LHH (Left Heart Hypoplasia), MVA (Mitral Valve Atresia), PFO (Patent Foramen Ovale), RHH (Right Heart Hypoplasia), TA (Truncus Arteriosus), (Tetralogy of Fallot), TVS (Tricuspid Valve Stenosis), VSD (Ventricular Septal Defect).