Table 2.
Literature search on studies of DNA methylation in placenta tissue and hyperglycaemia and dyslipidemia in pregnancy.
| Sample size | Method | Genes | Results | Influence of foetal sex | Authors, year, PMID |
|---|---|---|---|---|---|
| Dyslipidemia | |||||
| Placenta, 3rd trimester | |||||
| 262 | 450k EWAS | STK11, MOGAT2, DHRS12, BRD1, ECI2, SRM, ALX4, MICA, RPTOR, FAAH, HECTD2 | 11 CpGs in 11 genes associated with maternal dyslipidemia (after FDR). | Adjusted for foetal sex | Ouidir et al, 2020 [119] |
| 69 | PS | LDLR, LRP1, SCARB1 | Maternal cholesterol changes were negatively associated with LDLR DNAm and positively associated with LRP1 DNAm. LDLR and LRP1 DNAm was associated with cord blood triglyceride and leptin levels. Mediation analysis supported a causal relationship between cholesterol changes, LRP1 DNAm, and cord blood leptin level. | Adjusted for foetal sex | Guay et al, 2019 [120] |
| 262 | 450k EWAS | The Horvath Clock | Low maternal HDL cholesterol associated with accelerated placental epigenetic ageing among mothers with normal pre-pregnancy weight and a female foetus. | Adjusted and stratified for foetal sex | Shrestha et al, 2019 [55] |
| Hyperglycaemia | |||||
| Placenta, 3rd trimester | |||||
| 259 | EPIC EWAS | LEP | Maternal glycaemia associated with LEP DNAm, neonatal leptinemia, and adiposity and skinfolds at age 3 years. DNAm levels at cg15758240 mediates 0.8% of the association between maternal glycaemia and neonatal leptinemia. | Adjusted for foetal sex X/Y probes removed |
Gagné-Ouellet et al, 2020 [50] |
| 430 | EPIC EWAS |
CHRNA4, MICALL2/ UNCX, DLGAP2, ENTPD2, DP1P |
DNAm at 188 CpG sites was associated with Matsuda index (after FDR). Mendelian randomization analyses found five loci where DNAm may causally influence maternal insulin sensitivity, including the maternally imprinted gene DLGAP2. | Adjusted for foetal sex X/Y probes removed |
Hivert et al, 2020 [65] |
| 12 decreased GI 12 increased GI |
PS, 450k EWAS |
PLIN1, CPT1B, SSTR4, CIDEA | Negative association between DNAm and miRNA expression*. | No data on foetal sex X/Y probes removed |
Yan et al, 2019 [121] |
| 448 | EPIC EWAS | PDE4B, TNFRSF1B, LDLR, BLM | DNAm of PDE4B, NFRSF1B, LDLR, and BLM associated (after FDR) with 2 hr glucose post OGTT. DNAm and mRNA expression of PDE4B, TNFRSF1B and LDLR was negatively correlated. In an independent replication the results were consistent in direction. | Adjusted for foetal sexX/Y probes removed | Cardenas et al, 2018 [122] |
| 24 GDM 34 Ctrl |
PS | PGC1A | In combined groups, DNAm associated positively with fasting, 1 hr, and 2 hr glucose levels post OGTT. | Adjusted for foetal sex | Xie et al, 2015 [47] |
| 34 IGT 106 NGT |
PS | IGF1R, IGFBP3, IGF1, INSR | DNAm of IGF1R and IGFBP3 were lower in IGT compared to NGT and associated negatively with fasting (IGF1R) and 2 hr glucose levels (IGF1R and IGFBP3) post OGTT. | Adjusted for foetal sex | Desgagné et al, 2014 [123] |
| 26 IGT 74 NGT |
PS | ABCA1 | DNAm at maternal side was positively associated with 2 hr glucose levels post OGTT. | Adjusted for foetal sex (partly) | Houde et al, 2013 [124] |
| 98 | PS | ADIPOQ | Foetal side DNAm associated negatively with 2hr glucose post OGTT. Maternal side DNAm associated negatively with HOMA-IR. DNAm at both sides associated negatively with maternal adiponectin levels | No data on foetal sex | Bouchard et al, 2012 [53] |
If FDR is not stated in the table, it was not stated in the paper.
*Yan et al did not include continuous data on glycaemic index (GI).
Abbreviations: DNAm: DNA methylation, GI: glycaemic index, OGTT: oral glucose tolerance test, IGT: impaired glucose tolerance, NGT: Normal glucose tolerance, FDR: false discovery rate, EWAS: epigenome wide association study, PS: pyrosequencing.