Table 1.
The methodological characteristics of studies that compared epigenetics changes between GDM patients and controls.
| Authors | Study Design | n | Method Used for Epigenetic Analysis | Biological Sample Used for Epigenetic Analysis | Genes or Proteins Affected | GDM Criteria |
|---|---|---|---|---|---|---|
| Lesseur, et al. [18] | Cohort | 47 GDM and 488 non GDM women | BSP | Placental tissue (fetal side) | LEP | Not reported |
| Gagné-Ouellet, et al. [19] | Cohort | 12 GDM and 250 non GDM women | Infinium MethylationEPIC BeadChip |
Placental tissue (fetal side) | LEP | Canadian Diabetes Association (year not reported) |
| Bouchart, et al. [20] | Cohort | 31 IGT women and 67 NGT women | BSP | Placental tissue from both maternal and fetal sides | ADIPOQ | Only 2 women from IGT group fulfilled the ADA 2009 criteria for GDM. Women were classified as having IGT with a 2-h post-OGTT glucose level ≥7.8 mmol/L |
| Blazevic, et al. [21] | Case-control | 18 GDM and 32 NGT | DBS | Placental tissue (fetal side) | SLC6A4 | IADPSG 2010 |
| Côté, et al. [22] | Cohort | 33 GDM and 100 NGT | BSP | Placental tissue (fetal side) | PRDM16, BMP7, CTBP2 and PPARGC1α | WHO 2013 |
| Wang, et al. [23] | Case-control | 18 GDM and 32 control | DBS | Placental tissue (fetal side) | PPARGC1α and PDX1 | Two step: Step 1: 50 g GCT Cutoff value (mmol/L): ≥7.8 Step 2: 100 g OGTT Cutoff value (mmol/L) Fasting: >5.6 1 h: >10.3 2 h: >8.6 3 h: >6.7 Diagnosed: 4 abnormalities |
| Houde, et al. [24] | Cohort | 27 GDM and 99 NGT | Illumina Human Methylation 450 DNA Analysis Beadchip and BSP | Placental tissue (fetal side) | LPL | WHO 2013 |
| Qiu, et al. [25] | Case-control | 60 GDM and 60 controls | qRT-PCR | Plasma from maternal peripheral blood and placenta | miR-518d, NF-κB, COX-2, TNF-α, IL-1β, IL-6 and PPARα | Not reported |
| Sun, et al. [26] | Case-control | 204 GDM and 202 control | qRT-PCR | Placental tissue | miR-29b and HIF3A | WHO 2013 |
| Cao, et al. [27] | Case-control | 193 GDM and 202 control | qRT-PCR | Placental tissue | miR-98, MECP2 and TRPC3 | Not reported |
| Ding, et al. [28] | Case-control | Discovery stage: 8 GDM and 8 controls Validation stage: 28 GDM and 26 control |
RNA-seq and qRT-PCR | Placental tissue | miR-202-5p, miR-138-5p, miR-210-5p, miR-3158-5p, miR-4732-3p, TBL1X, NOTUM, FRMD4A, SLC16A2, CLDN19, CCL18, HTRA1 and SLC39A6 | IADPSG 2010 |
| Hepp, et al. [29] | Case-control | 40 GDM and 40 controls | Immunohistochemistry and double immunofluorescence | Placental tissue (maternal side) | Histones H3 | GSDB 2011 |
| Rancourt, et al. [30] | Nested case-control | 19 GDM and 22 controls matched for maternal age, socio-economic status, ethnic origin, parity and pre-pregnancy BMI | BSP | Subcutaneous and visceral adipose tissues | TNF-α and SOCS3 | GSGO 2018 |
| Ott, et al. [31] | Nested case-control | 25 GDM and 30 controls matched for maternal age, ethnic origin, socio-economic status, parity and pre-pregnancy BMI | BSP | DNA from blood cells, subcutaneous and visceral adipose tissue | ADIPOQ | GSGO 2018 |
| Deng, et al. [32] | Case-control | Discovery stage: 3 GDM and 3 controls Validation stage: 26 GDM and 24 controls |
Illumina Human Methylation 450 k DNA Analysis Beadchip and BSP | Visceral omental adipose tissue | HLA-DMB, MSLN, and HSPA6 | WHO 2013 |
| Shi, et al. [33] | Case-control | Discovery stage: 3 GDM and 3 controls. Validation stage: 13 GDM and 13 controls. |
AFFX miRNA expression chips and qRT-PCR | Omental adipose tissue | miR-222, ERα and GLUT4 | ADA 2006 |
| Dias, et al. [34] | Case-control | 12 GDM and 12 controls matched for age, gestational age and BMI. | Illumina’s Infinium HumanMethylationEPIC Bead Chip | DNA from maternal peripheral blood | SLC9A3, MEA1;KLHDC3, CAMTA1 and RASA3 | IADPSG 2010 |
| Wu, et al. [35] | Cohort | 11 GDM and 11 controls matched for age, BMI, ethnicity, smoking, treatment, and folate supplementation | Illumina HumanMethylation450 BeadChip and BSP | DNA from maternal peripheral blood | COPS8, PIK3R5, HAAO, C5orf34 and CCDC124 | Not reported |
| Michalczy, et al. [36] | Cohort | 27 pregnant women classified as non-diabetic (7 women), GDM who did not develop T2DM (8 women), GDM who developed T2DM (6 women), and women with pre-existing T2DM (6 women) | Western blot | White blood cells from maternal peripheral blood | Histones H3 | IADPSG 2010 |
| Zhao, et al. [37] | Nested case-control | Discovery stage: 24 GDM and 24 controls. Internal validation: 36 GDM and 36 controls. Two different external validations: 32 GDM and 32 controls in total. In all stages, the groups were matched for age, BMI, gestational age, and gravidity |
TaqMan low density arrays Chips and qRT-PCR | Serum from maternal peripheral blood | miR-29a, miR-222, INSIG1 and PCK2 | ADA 2004 |
| Zhu, et al. [38] | Case-control | 10 GDM and 10 controls matched for maternal age and gestational age | Ion Torrent high-throughput sequencing technology and qRT-PCR | Plasma from maternal peripheral blood | hsa-miR-16-5p, hsa-miR-17-5p, hsa-miR-19a-3p, hsa-miR-19b-3p, hsa-miR-20a-5p, MAPK-1, IRS-1, IRS-2, SOS-1, SMAD5, SMAD4 and AKT3 | ADA 2011 |
| Pheiffer, et al. [39] | Case-control | 28 GDM and 53 controls matched for age and BMI | qRT-PCR | Serum from maternal peripheral blood | hsa-miR-20a-5p | IADPSG 2010 |
BMI, body mass index; NGT, normal glucose tolerance; BSP, bisulfite pyrosequencing; DBS, direct bisulfite sequencing; qRT-PCR, quantitative reverse transcription—polymerase chain reaction; LEP, leptin; ADIPOQ, adiponectin; SLC6A4, solute carrier family 6 member 4; PRDM16, PR domain-containing protein 16; BMP7, bone morphogenetic protein 7; CTBP2, C-terminal binding protein 2; PPARGC1α, peroxisome proliferator-activated receptor-gamma, co-activator 1, alpha; PDX1, pancreatic and duodenal homeobox l; LPL, lipoprotein lipase; NF-κB, nuclear factor-kappa B; COX-2, cytochrome C oxidase subunit II; TNF-α, tumoral necrosis factor alpha; IL-1β, interleukin 1 beta; IL-6, interleukin 6; PPARα, peroxisome proliferator-activated receptor alpha; HIF3A, hypoxia inducible factors 3A; MECP2, methyl CpG binding protein 2; TRPC3, transient receptor potential 3; TBL1X, transducing beta like 1 X-linked; NOTUM, notum, palmitoleoyl-protein carboxylesterase; FRMD4A, FERM domain containing 4A; SLC39A6, solute carrier family 39 member 6; SLC16A2, solute carrier family 16 member 2; CLDN19, claudin 19; CCL18, C-C motif chemokine ligand 18; HTRA1, HtrA serine peptidase 1; SOCS3, suppressor of cytokine signaling 3; HLA-DMB, major histocompatibility complex, class II, DM beta; MSLN, mesothelin; HSPA6, heat shock protein family A (Hsp70) member 6; ERα, estrogen receptor alpha; GLUT4, glucose transporter 4; SLC9A3, solute carrier family 9 member A3; MEA1;KLHDC3, male-enhanced antigen 1; kelch domain-containing protein 3; CAMTA1, calmodulin binding transcription activator 1; RASA3, RAS P21 protein activator 3; COPS8, constitutive photomorphogenic homolog subunit 8; PIK3R5, phosphoinositide-3-kinase, regulatory subunit 5; HAAO, 3-hydroxyanthranilate 3,4-dioxygenase; C5orf34, chromosome 5 open reading frame 34; CCDC124, coiled-coil domain containing 124; INSIG1, insulin-induced gene 1; PCK2, phosphoenolpyruvate carboxy kinase 2; MAPK-1, mitogen-activated protein kinase 1; IRS-1, insulin receptor substrate 1; IRS-2, insulin receptor substrate 2; SOS-1, SOS Ras/Rac guanine nucleotide exchange factor 1; SMAD5, SMAD family member 5; SMAD4, SMAD family member 4; AKT3, AKT serine/threonine kinase 3; GSDB, German Society for Diabetes Mellitus; GSGO 2018, German Society for Gynecology and Obstetrics 2018; GCT, glucose challenge test; ADA, American Diabetes Association; WHO, World Health Organization; IADPSG, International Association of Diabetes and Pregnancy Study Group; IGT, impaired glucose tolerance.